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128-513: Symptoms from CTE do not typically appear in a subject until many years after the initial injuries, and a conclusive diagnosis of the disease can only be achieved through autopsy . In the years since its inception, the BU CTE Center and Brain Bank has devoted the majority of its time and effort into researching methods for diagnosing CTE in living subjects and developing potential treatments for

256-417: A body bag or evidence sheet. A new body bag is used for each body to ensure that only evidence from that body is contained within the bag. Evidence sheets are an alternative way to transport the body. An evidence sheet is a sterile sheet that covers the body when it is moved. If it is believed there may be any significant evidence on the hands, for example, gunshot residue or skin under the fingernails ,

384-442: A polyglutamine (polyQ) tract . Diseases associated with such mutations are known as trinucleotide repeat disorders . Polyglutamine repeats typically cause dominant pathogenesis. Extra glutamine residues can acquire toxic properties through a variety of ways, including irregular protein folding and degradation pathways, altered subcellular localization, and abnormal interactions with other cellular proteins. PolyQ studies often use

512-412: A cause of class I errors. While patients with abdominal pathologic conditions generally complained of abdominal pain, results of an examination of the abdomen were considered unremarkable in most patients, and the symptom was not pursued". There are four main types of autopsy: A forensic autopsy is used to determine the cause, mode, and manner of death. Forensic science involves the application of

640-644: A central resource for the collection and distribution of brain and brain tissue samples. Brain donors may donate their brains after death to aid in the understanding of neural diseases. Brain banks differ from other organ banks in that donated brains will only be used for research purposes, and will not be given to other individuals. Dr. Ann McKee acts is the Director for the VA-BU-CLF Brain Bank and Boston University CTE Center, leading her team of researchers during group and individual case studies. McKee

768-460: A classic case of CTE, as multiple groupings of the tau protein could be seen in frontal lobes. These p-tau deposits developed in close proximity to small blood vessels in the brain and spread to areas that control perception, memory, and emotion. The discovery from Hernandez's autopsy began to shed new light on the impact of CTE in American football players, as well as other athletes. The degree of

896-430: A conflation of many criteria: clinical signs and symptoms, evaluations of the eye, electroencephalograms (EEG), and brain magnetic resonance imaging (MRI) results. The diagnosis provided by these results are corroborated by genetic and biochemical testing. No effective treatments were available to prevent the disease from being widespread before the past few years. In recent years, more models have been created to expedite

1024-422: A deceased individual. It is an alternative to medical autopsies, where radiographs are used, for example, Magnetic resonance imaging (MRI) and Computed tomography ( CT scan ) which produce radiographic images in order to determine the cause of death, the nature, and the manner of death, without dissecting the deceased. It can also be used in the identification of the deceased. This method is helpful in determining

1152-451: A fifth of consumed oxygen, and reactive oxygen species produced by oxidative metabolism are a major source of DNA damage in the brain . Damage to a cell's DNA is particularly harmful because DNA is the blueprint for protein production and unlike other molecules it cannot simply be replaced by re-synthesis. The vulnerability of post-mitotic neurons to DNA damage (such as oxidative lesions or certain types of DNA strand breaks), coupled with

1280-425: A fragment from a larger protein called amyloid precursor protein (APP), a transmembrane protein that penetrates through the neuron's membrane. APP appears to play roles in normal neuron growth, survival and post-injury repair. APP is cleaved into smaller fragments by enzymes such as gamma secretase and beta secretase . One of these fragments gives rise to fibrils of amyloid beta which can self-assemble into

1408-939: A gradual decline in the activities of repair mechanisms , could lead to accumulation of DNA damage with age and contribute to brain aging and neurodegeneration. DNA single-strand breaks are common and are associated with the neurodegenerative disease ataxia- oculomotor apraxia . Increased oxidative DNA damage in the brain is associated with Alzheimer's disease and Parkinson's disease . Defective DNA repair has been linked to neurodegenerative disorders such as Alzheimer's disease, amyotrophic lateral sclerosis , ataxia telangiectasia , Cockayne syndrome , Parkinson's disease and xeroderma pigmentosum . Axonal swelling, and axonal spheroids have been observed in many different neurodegenerative diseases. This suggests that defective axons are not only present in diseased neurons, but also that they may cause certain pathological insult due to accumulation of organelles. Axonal transport can be disrupted by

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1536-444: A pillow in an open casket funeral . The scalp is pulled away from the skull in two flaps with the front flap going over the face and the rear flap over the back of the neck. The skull is then cut with a circular (or semicircular) bladed reciprocating saw to create a "cap" that can be pulled off, exposing the brain. The brain is then observed in situ. Then the brain's connections to the cranial nerves and spinal cord are severed, and

1664-412: A poison) and their quantity. Because post-mortem deterioration of the body, together with the gravitational pooling of bodily fluids, will necessarily alter the bodily environment, toxicology tests may overestimate, rather than underestimate, the quantity of the suspected chemical. Following an in-depth examination of all the evidence , a medical examiner or coroner will assign a manner of death from

1792-670: A public dissection of the body of a former criminal. He asserted and articulated the bones, this became the world's oldest surviving anatomical preparation. It is still displayed at the Anatomical Museum at the University of Basel. In the mid-1800s, Carl von Rokitansky and colleagues at the Second Vienna Medical School began to undertake dissections as a means to improve diagnostic medicine. Neurodegeneration A neurodegenerative disease

1920-561: A reaction termed transamidation or crosslinking . Transglutaminase binding of these proteins and peptides make them clump together. The resulting structures are turned extremely resistant to chemical and mechanical disruption. Most relevant human neurodegenerative diseases share the property of having abnormal structures made up of proteins and peptides . Each of these neurodegenerative diseases have one (or several) specific main protein or peptide. In Alzheimer's disease , these are amyloid-beta and tau . In Parkinson's disease, it

2048-469: A role in this disease mechanism. Impaired axonal transport of alpha-synuclein may also lead to its accumulation in Lewy bodies. Experiments have revealed reduced transport rates of both wild-type and two familial Parkinson's disease-associated mutant alpha-synucleins through axons of cultured neurons. Membrane damage by alpha-synuclein could be another Parkinson's disease mechanism. The main known risk factor

2176-443: A separate paper sack is put around each hand and taped shut around the wrist. There are two parts to the physical examination of the body: the external and internal examination. Toxicology , biochemical tests or genetic testing / molecular autopsy often supplement these and frequently assist the pathologist in assigning the cause or causes of death. At many institutions, the person responsible for handling, cleaning, and moving

2304-622: A significant brain injury while playing football at Harvard University. Nowinski partnered with researchers from Boston University to create the VA-BU-CLF Brain Bank. Lisa McHale currently acts as the director of family relations for the VA-BU-CLF Brain Bank, working with families of former athletes to help them understand CTE and the mission of the Boston University CTE Center. McHale joined the Concussion Legacy Foundation in 2010, first acting as

2432-467: A significant number of non-MIs were MIs. A systematic review of studies of the autopsy calculated that in about 25% of autopsies, a major diagnostic error will be revealed. However, this rate has decreased over time and the study projects that in a contemporary US institution, 8.4% to 24.4% of autopsies will detect major diagnostic errors. A large meta-analysis suggested that approximately one-third of death certificates are incorrect and that half of

2560-399: A spectrum based on the degree of inflammation, a majority of patients experience early relapsing and remitting episodes of neuronal deterioration following a period of recovery. Some of these individuals may transition to a more linear progression of the disease, while about 15% of others begin with a progressive course on the onset of multiple sclerosis. The inflammatory response contributes to

2688-516: A subset of patients with familial ALS. More recently, TAR DNA-binding protein 43 (TDP-43) and Fused in Sarcoma (FUS) protein aggregates have been implicated in some cases of the disease, and a mutation in chromosome 9 ( C9orf72 ) is thought to be the most common known cause of sporadic ALS. Early diagnosis of ALS is harder than with other neurodegenerative diseases as there are no highly effective means of determining its early onset. Currently, there

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2816-591: A variety of animal models because there is such a clearly defined trigger – repeat expansion. Extensive research has been done using the models of nematode ( C. elegans ), and fruit fly ( Drosophila ), mice, and non-human primates. Nine inherited neurodegenerative diseases are caused by the expansion of the CAG trinucleotide and polyQ tract, including Huntington's disease and the spinocerebellar ataxias . The presence of epigenetic modifications for certain genes has been demonstrated in this type of pathology. An example

2944-690: A variety of mechanisms including damage to: kinesin and cytoplasmic dynein , microtubules , cargoes, and mitochondria . When axonal transport is severely disrupted a degenerative pathway known as Wallerian-like degeneration is often triggered. Programmed cell death (PCD) is death of a cell in any form, mediated by an intracellular program. This process can be activated in neurodegenerative diseases including Parkinson's disease, amytrophic lateral sclerosis, Alzheimer's disease and Huntington's disease. PCD observed in neurodegenerative diseases may be directly pathogenic; alternatively, PCD may occur in response to other injury or disease processes. Apoptosis

3072-450: A wide range of sports. The majority of the reported CTE cases were former boxers (85%), but the study also included cases from former American football players, soccer players, and wrestlers . The study was primarily conducted to develop a more accurate clinical presentation of CTE in the brain. By studying the brains of former athletes whose sports commonly involved blows to the head, the researchers were able to identify how CTE looked in

3200-491: Is FKBP5 gene, which progressively increases its expression with age and has been related to Braak staging and increased tau pathology both in vitro and in mouse models of AD. Several neurodegenerative diseases are classified as proteopathies as they are associated with the aggregation of misfolded proteins . Protein toxicity is one of the key mechanisms of many neurodegenrative diseases. Parkinson's disease and Huntington's disease are both late-onset and associated with

3328-777: Is aging . Mitochondrial DNA mutations as well as oxidative stress both contribute to aging. Many of these diseases are late-onset, meaning there is some factor that changes as a person ages for each disease. One constant factor is that in each disease, neurons gradually lose function as the disease progresses with age. It has been proposed that DNA damage accumulation provides the underlying causative link between aging and neurodegenerative disease. About 20–40% of healthy people between 60 and 78 years old experience discernable decrements in cognitive performance in several domains including working, spatial, and episodic memory, and processing speed. A study using electronic health records indicates that 45 (with 22 of these being replicated with

3456-573: Is alpha-synuclein . In Huntington's disease, it is huntingtin . Transglutaminase substrates : Amyloid-beta , tau , alpha-synuclein and huntingtin have been proved to be substrates of transglutaminases in vitro or in vivo, that is, they can be bonded by trasglutaminases by covalent bonds to each other and potentially to any other transglutaminase substrate in the brain. Transglutaminase augmented expression: It has been proved that in these neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, and Huntington's disease)

3584-456: Is a form of programmed cell death in multicellular organisms. It is one of the main types of programmed cell death (PCD) and involves a series of biochemical events leading to a characteristic cell morphology and death. Caspases (cysteine-aspartic acid proteases) cleave at very specific amino acid residues. There are two types of caspases: initiators and effectors . Initiator caspases cleave inactive forms of effector caspases. This activates

3712-438: Is a rare neurodegenerative disorder characterized by the gradual loss of both upper motor neurons (UMNs) and lower motor neurons (LMNs). Although initial symptoms may vary, most patients develop skeletal muscle weakness that progresses to involve the entire body. The precise etiology of ALS remains unknown. In 1993, missense mutations in the gene encoding the antioxidant enzyme superoxide dismutase 1 (SOD1) were discovered in

3840-479: Is a source of controversy among medical professionals. The gut microbiome might play a role in the diagnosis of PD, and research suggests various ways that could revolutionize the future of PD treatment. Huntington's disease (HD) is a rare autosomal dominant neurodegenerative disorder caused by mutations in the huntingtin gene (HTT) . HD is characterized by loss of medium spiny neurons and astrogliosis . The first brain region to be substantially affected

3968-461: Is age. Mutations in genes such as α-synuclein (SNCA), leucine-rich repeat kinase 2 (LRRK2), glucocerebrosidase (GBA), and tau protein (MAPT) can also cause hereditary PD or increase PD risk. While PD is the second most common neurodegenerative disorder, problems with diagnoses still persist. Problems with the sense of smell is a widespread symptom of Parkinson's disease (PD), however, some neurologists question its efficacy. This assessment method

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4096-485: Is aided in directing the Brain Bank by Dr. Chris Nowinski, CEO of the Concussion Legacy Foundation, and Lisa McHale, who acts as the Bank's director for family relations. When the VA-BU-CLF Brain Bank formally opened in 2008, it became the first tissue repository in the world fully dedicated to the study of CTE. The Brain Bank continues to lead the field of CTE study, as it remains the largest brain tissue repository in

4224-413: Is caused by the progressive loss of neurons , in the process known as neurodegeneration . Neuronal damage may also ultimately result in their death . Neurodegenerative diseases include amyotrophic lateral sclerosis , multiple sclerosis , Parkinson's disease , Alzheimer's disease , Huntington's disease , multiple system atrophy , tauopathies , and prion diseases . Neurodegeneration can be found in

4352-425: Is characterized by motor impairment, epilepsy , dementia , vision loss, and shortened lifespan. A loss of vision is common first sign of Batten disease. Loss of vision is typically preceded by cognitive and behavioral changes, seizures, and loss of the ability to walk. It is common for people to establish cardiac arrhythmias and difficulties eating food as the disease progresses. Batten disease diagnosis depends on

4480-405: Is collected from the external surfaces of the body. Ultraviolet light may also be used to search body surfaces for any evidence not easily visible to the naked eye. Samples of hair , nails , and the like are taken, and the body may also be radiographically imaged . Once the external evidence is collected, the body is removed from the bag, undressed, and any wounds present are examined. The body

4608-400: Is deleterious to the cell and would eventually lead to cell death. Apart from tubular structures, alpha-synuclein can also form lipoprotein nanoparticles similar to apolipoproteins. The most common form of cell death in neurodegeneration is through the intrinsic mitochondrial apoptotic pathway. This pathway controls the activation of caspase-9 by regulating the release of cytochrome c from

4736-456: Is hypothesized that defects in autophagy could be a common mechanism of neurodegeneration. PCD can also occur via non-apoptotic processes, also known as Type III or cytoplasmic cell death. For example, type III PCD might be caused by trophotoxicity, or hyperactivation of trophic factor receptors. Cytotoxins that induce PCD can cause necrosis at low concentrations, or aponecrosis (combination of apoptosis and necrosis) at higher concentrations. It

4864-414: Is no need for any incision to be made, which will be visible after completion of the examination when the deceased is dressed in a shroud. In all of the above cases, the incision then extends all the way down to the pubic bone (making a deviation to either side of the navel) and avoiding, where possible, transecting any scars that may be present. Bleeding from the cuts is minimal, or non-existent because

4992-445: Is not made. Autopsies are used in clinical medicine to identify a medical error or a previously unnoticed condition that may endanger the living, such as infectious diseases or exposure to hazardous materials . A study that focused on myocardial infarction (heart attack) as a cause of death found significant errors of omission and commission, i.e. a sizable number of cases ascribed to myocardial infarctions (MIs) were not MIs and

5120-449: Is primarily characterized by death of dopaminergic neurons in the substantia nigra , a region of the midbrain . The cause of this selective cell death is unknown. Notably, alpha-synuclein - ubiquitin complexes and aggregates are observed to accumulate in Lewy bodies within affected neurons. It is thought that defects in protein transport machinery and regulation, such as RAB1 , may play

5248-502: Is proposed to be due to the release of antigens such as myelin oligodendrocyte glycoprotein , myelin basic protein , and proteolipid protein , causing an autoimmune response. This sets off a cascade of signaling molecules that result in T cells, B cells, and macrophages to cross the blood-brain barrier and attack myelin on neuronal axons leading to inflammation. Further release of antigens drives subsequent degeneration causing increased inflammation. Multiple sclerosis presents itself as

Boston University CTE Center and Brain Bank - Misplaced Pages Continue

5376-448: Is research being done regarding the diagnosis of ALS through upper motor neuron tests. The Penn Upper Motor Neuron Score (PUMNS) consists of 28 criteria with a score range of 0–32. A higher score indicates a higher level of burden present on the upper motor neurons. The PUMNS has proven quite effective in determining the burden that exists on upper motor neurons in affected patients. Independent research provided in vitro evidence that

5504-451: Is sometimes termed a "view and grant". The principle behind this is that the medical records, history of the deceased and circumstances of death have all indicated as to the cause and manner of death without the need for an internal examination. If not already in place, a plastic or rubber brick called a "head block" is placed under the shoulders of the corpse; hyperflexion of the neck makes the spine arch backward while stretching and pushing

5632-401: Is still unclear exactly what combination of apoptosis, non-apoptosis, and necrosis causes different kinds of aponecrosis. Transglutaminases are human enzymes ubiquitously present in the human body and in the brain in particular. The main function of transglutaminases is bind proteins and peptides intra- and intermolecularly, by a type of covalent bonds termed isopeptide bonds , in

5760-400: Is subpar, and better methods need to be utilized for various aspects of clinical diagnoses. Alzheimer's has a 20% misdiagnosis rate. AD pathology is primarily characterized by the presence of amyloid plaques and neurofibrillary tangles . Plaques are made up of small peptides , typically 39–43 amino acids in length, called amyloid beta (also written as A-beta or Aβ). Amyloid beta is

5888-449: Is the striatum , followed by degeneration of the frontal and temporal cortices. The striatum's subthalamic nuclei send control signals to the globus pallidus , which initiates and modulates motion. The weaker signals from subthalamic nuclei thus cause reduced initiation and modulation of movement, resulting in the characteristic movements of the disorder, notably chorea . Huntington's disease presents itself later in life even though

6016-511: Is the Director of the Boston University CTE Center and a professor of neurology and pathology at the Boston University School of Medicine. Her research focuses on CTE and the late effects of neurodegeneration . Along with her colleagues, McKee has conducted several research studies involving traumatic brain injuries in sports and military situations, and the long-term effects of these injuries. While her largest project has been

6144-400: Is the common name for a group of lysosomal storage disorders known as neuronal ceroid lipofuscinoses (NCLs) – each caused by a specific gene mutation, of which there are thirteen. Since Batten disease is quite rare, its worldwide prevalence is about 1 in every 100,000 live births. In North America, NCL3 disease (juvenile NCL) typically manifests between the ages of 4 and 7. Batten disease

6272-592: Is the examination of murder victims, especially when medical examiners are looking for signs of death or the murder method, such as bullet wounds and exit points, signs of strangulation , or traces of poison . Some religions including Judaism and Islam usually discourage the performing of autopsies on their adherents. Organizations such as ZAKA in Israel and Misaskim in the United States generally guide families on how to ensure that an unnecessary autopsy

6400-466: Is the most common neurodegenerative disease. Even with billions of dollars being used to find a treatment for Alzheimer's disease, no effective treatments have been found. Within clinical trials stable and effective AD therapeutic strategies have a 99.5% failure rate. Reasons for this failure rate include inappropriate drug doses, invalid target and participant selection, and inadequate knowledge of pathophysiology of AD. Currently, diagnoses of Alzheimer's

6528-417: Is the tau protein, that leads directly to the formation of the disease in the brain. This protein forms as a result of blows taken within the skull, resulting in rapid movement of the brain. By analyzing how and where this protein forms within the brain, researchers can potentially map the protein in living individuals, and predict the development of the disease. As research into the disease continues, leaders of

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6656-548: Is then cleaned, weighed, and measured in preparation for the internal examination. A general description of the body as regards ethnic group , sex , age, hair colour and length, eye colour , and other distinguishing features ( birthmarks , old scar tissue , moles , tattoos , etc.) is then made. A voice recorder or a standard examination form is normally used to record this information. In some countries, e.g. , Scotland, France, Germany, Russia, and Canada, an autopsy may comprise an external examination only. This concept

6784-413: Is used almost all of the time. The various organs are examined, weighed and tissue samples in the form of slices are taken. Even major blood vessels are cut open and inspected at this stage. Next, the stomach and intestinal contents are examined and weighed. This could be useful to find the cause and time of death, due to the natural passage of food through the bowel during digestion. The more area empty,

6912-506: The UK Biobank ) viral exposures can significantly elevate risks of neurodegenerative disease, including up to 15 years after infection. Many neurodegenerative diseases are caused by genetic mutations , most of which are located in completely unrelated genes. In many of the different diseases, the mutated gene has a common feature: a repeat of the CAG nucleotide triplet. CAG codes for the amino acid glutamine . A repeat of CAG results in

7040-469: The afterlife (as with the Egyptians, who removed the organs through tiny slits in the body). Notable Greek autopsists were Erasistratus and Herophilus of Chalcedon , who lived in 3rd century BCE Alexandria , but in general, autopsies were rare in ancient Greece. In 44 BCE, Julius Caesar was the subject of an official autopsy after his murder by rival senators, the physician's report noting that

7168-403: The cerebral cortex , most likely in the area between sulci . In the second stage of CTE, the tau protein is observed in multiple areas of the cerebral cortex, as the p-tau pathology begins to spread across sulci. In stage III CTE, the tau protein becomes widespread, with the greatest severity located in the frontal and temporal lobes . The p-tau groups in these regions are often concentrated in

7296-476: The chest upward to make it easier to incise. This gives the APT, or pathologist, maximum exposure to the trunk . After this is done, the internal examination begins. The internal examination consists of inspecting the internal organs of the body by dissection for evidence of trauma or other indications of the cause of death. For the internal examination there are a number of different approaches available: There

7424-454: The expression of the transglutaminase enzyme is increased. Presence of isopeptide bonds in these structures: The presence of isopeptide bonds (the result of the transglutaminase reaction) have been detected in the abnormal structures that are characteristic of these neurodegenerative diseases . Co-localization: Co-localization of transglutaminase mediated isopeptide bonds with these abnormal structures has been detected in

7552-453: The hilum . The right lung can then be similarly removed. The abdominal organs can be removed one by one after first examining their relationships and vessels. Most pathologists, however, prefer the organs to be removed all in one "block". Using dissection of the fascia, blunt dissection; using the fingers or hands and traction; the organs are dissected out in one piece for further inspection and sampling. During autopsies of infants, this method

7680-573: The mitochondrial intermembrane space . Reactive oxygen species (ROS) are normal byproducts of mitochondrial respiratory chain activity. ROS concentration is mediated by mitochondrial antioxidants such as manganese superoxide dismutase (SOD2) and glutathione peroxidase . Over production of ROS ( oxidative stress ) is a central feature of all neurodegenerative disorders. In addition to the generation of ROS, mitochondria are also involved with life-sustaining functions including calcium homeostasis, PCD, mitochondrial fission and fusion , lipid concentration of

7808-417: The pulmonary artery is opened in order to search for a blood clot. The heart can then be removed by cutting the inferior vena cava, the pulmonary veins, the aorta and pulmonary artery, and the superior vena cava . This method leaves the aortic arch intact, which will make things easier for the embalmer. The left lung is then easily accessible and can be removed by cutting the bronchus , artery, and vein at

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7936-491: The subcellular level, including atypical protein assemblies (like proteinopathy ) and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well. Within neurodegenerative diseases, it is estimated that 55 million people worldwide had dementia in 2019, and that by 2050 this figure will increase to 139 million people. The consequences of neurodegeneration can vary widely depending on

8064-618: The 17th century. The term "post-mortem" derives from the Latin post , 'after', and mortem , 'death'. It was first recorded in 1734. The term "necropsy" is derived from the Greek νεκρός 'death' and ὄψις ( opsis , 'sight, view'). The principal aims of an autopsy are to determine the cause of death , mode of death, manner of death , the state of health of the person before he or she died, and whether any medical diagnosis and treatment before death were appropriate. In most Western countries

8192-442: The Brain Bank grew, as the link between CTE and American football became clear. These increased donations allowed for a larger case study, which would give researchers an opportunity to paint a clearer picture of the disease in a brain. Each of the 202 deceased players had a history of brain trauma and experienced behavioral, mood, and cognitive symptoms during their lives. In addition, the most common cause of death among participants

8320-460: The CTE Center focuses its research on the formation of neurodegenerative diseases, including Post-Concussion Syndrome and CTE. During case studies, researchers at the CTE Center perform high-impact tests and in-depth autopsies on post-mortem brains to further understand the neuropathology and clinical presentation of CTE. These tests examine the effects of concussions and sub-concussive blows on

8448-415: The CTE Center. These results suggested CTE might be related to participation in football, and higher levels of play may increase the likelihood of the disease. In April 2017, former New England Patriots tight end Aaron Hernandez committed suicide in a jail cell at the age of 27. Hernandez's suicide occurred just months after he was convicted of first-degree murder and sentenced to life in prison without

8576-572: The CTE present in Hernandez's brain was unprecedented for someone so young. In the autopsy report from Boston University, Dr. McKee explains that Hernandez's brain was one of the most intact specimens her team had ever examined. McKee also notes that the damage to Hernandez's brain took years to develop, and was not the symptom of one incident. While the fear of CTE in American football players had grown after initial discoveries from Boston University, most of

8704-466: The Center's 2015 study, researchers from Boston University partnered with Stanford University to conduct autopsies on the brains of 202 deceased former American football players from multiple levels (high school, college, semi-pro, CFL, NFL ). Recruitment for this study began in 2008, after the establishment of the VA-BU-CLF Brain Bank. After the success of the 2015 American football case study, donations to

8832-665: The UK and worldwide has declined rapidly over the past 50 years. In the UK in 2013, only 0.7% of inpatient adult deaths were followed by consented autopsy. The autopsy rate in Germany is below 5% and thus much lower than in other countries in Europe. The governmental reimbursement is hardly sufficient to cover all the costs, so the medical journal Deutsches Ärzteblatt , issued by the German Medical Association , makes

8960-405: The UK is a modified version of this method, which is divided into four groups of organs. Although these are the two predominant evisceration techniques, in the UK variations on these are widespread. One method is described here: The pericardial sac is opened to view the heart. Blood for chemical analysis may be removed from the inferior vena cava or the pulmonary veins. Before removing the heart,

9088-501: The UK, following the Human Tissue Act 2004 all organs and tissue must be returned to the body unless permission is given by the family to retain any tissue for further investigation. Normally the internal body cavity is lined with cotton, wool, or a similar material, and the organs are then placed into a plastic bag to prevent leakage and are returned to the body cavity. The chest flaps are then closed and sewn back together and

9216-403: The VA-BU-CLF Brain Bank hope to utilize their findings to develop methods for treating and preventing the disease. Autopsy An autopsy (also referred to as post-mortem examination , obduction , necropsy , or autopsia cadaverum ) is a surgical procedure that consists of a thorough examination of a corpse by dissection to determine the cause, mode, and manner of death ; or

9344-537: The Volunteer and Family Coordinator. McHale has personal experience with families dealing with the effects of CTE, as her husband Tom McHale , a former American football player, passed away in 2008 due to complications from the disease. In 2009, Dr. McKee and her team of researchers from Boston University published their first CTE study. This publication discussed 47 instances of neuropathological deterioration determined to be CTE. The study involved former athletes from

9472-723: The accumulation of intracellular toxic proteins. Diseases caused by the aggregation of proteins are known as proteopathies , and they are primarily caused by aggregates in the following structures: There are two main avenues eukaryotic cells use to remove troublesome proteins or organelles: Damage to the membranes of organelles by monomeric or oligomeric proteins could also contribute to these diseases. Alpha-synuclein can damage membranes by inducing membrane curvature, and cause extensive tubulation and vesiculation when incubated with artificial phospholipid vesicles. The tubes formed from these lipid vesicles consist of both micellar as well as bilayer tubes. Extensive induction of membrane curvature

9600-760: The autopsies performed produced findings that were not suspected before the person died. Also, it is thought that over one-fifth of unexpected findings can only be diagnosed histologically , i.e. , by biopsy or autopsy, and that approximately one-quarter of unexpected findings, or 5% of all findings, are major and can similarly only be diagnosed from tissue. One study found that (out of 694 diagnoses) "Autopsies revealed 171 missed diagnoses, including 21 cancers, 12 strokes, 11 myocardial infarctions, 10 pulmonary emboli, and 9 endocarditis, among others". Focusing on intubated patients, one study found "abdominal pathologic conditions – abscesses, bowel perforations, or infarction – were as frequent as pulmonary emboli as

9728-408: The autopsy is the reconstitution of the body such that it can be viewed, if desired, by relatives of the deceased following the procedure. After the examination, the body has an open and empty thoracic cavity with chest flaps open on both sides; the top of the skull is missing, and the skull flaps are pulled over the face and neck. It is unusual to examine the face, arms, hands or legs internally. In

9856-502: The autopsy of brains of patients with these diseases. The process of neurodegeneration is not well understood, so the diseases that stem from it have, as yet, no cures. In the search for effective treatments (as opposed to palliative care ), investigators employ animal models of disease to test potential therapeutic agents. Model organisms provide an inexpensive and relatively quick means to perform two main functions: target identification and target validation. Together, these help show

9984-531: The body is called a diener , the German word for servant . In the UK this role is performed by an Anatomical Pathology Technician (APT), who will also assist the pathologist in eviscerating the body and reconstruction after the autopsy. After the body is received, it is first photographed . The examiner then notes the kind of clothes - if any - and their position on the body before they are removed. Next, any evidence such as residue, flakes of paint, or other material

10112-509: The body is dissected and an internal examination is conducted. Permission from next of kin may be required for internal autopsy in some cases. Once an internal autopsy is complete, the body is reconstituted by sewing it back together. The term "autopsy" derives from the Ancient Greek αὐτοψία autopsia , "to see for oneself", derived from αὐτός ( autos , "oneself") and ὄψις ( opsis , "sight, view"). The word has been in use since around

10240-538: The body, by filling the veins with wax and metals. Until the 20th century, it was thought that the modern autopsy process derived from the anatomists of the Renaissance . Giovanni Battista Morgagni (1682–1771), celebrated as the father of anatomical pathology , wrote the first exhaustive work on pathology, De Sedibus et Causis Morborum per Anatomen Indagatis (The Seats and Causes of Diseases Investigated by Anatomy, 1769). In 1543, Andreas Vesalius conducted

10368-431: The brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at

10496-423: The brain is lifted out of the skull for further examination. If the brain needs to be preserved before being inspected, it is contained in a large container of formalin (15 percent solution of formaldehyde gas in buffered water ) for at least two, but preferably four weeks. This not only preserves the brain, but also makes it firmer, allowing easier handling without corrupting the tissue. An important component of

10624-414: The brain of a former athlete. Through in-depth autopsies, the researchers observed the formation of proteins in the brain that caused initial brain cell decay, ultimately leading to CTE in the brain. The first major American football study conducted by the BU CTE Center involved the donated brains of 79 former NFL players. This study was released in 2015 and detailed the autopsies performed by researchers on

10752-474: The brain, specifically as they relate to the development of CTE. The Center's ultimate goal is to develop a test that would definitively diagnose CTE in a living subject. In order to accomplish this, researchers at Boston University made it a priority to study as many post-mortem brains as possible, which led to the formation of the VA-BU-CLF Brain Bank. Currently, the Brain Bank contains over 600 brains , including 325 brains that have been diagnosed with CTE since

10880-472: The cases featured older players who had been retired for several decades before passing away. With the study of Hernandez's brain, a new push was established to attempt to find a method for diagnosing the disease in living subjects, and ultimately develop ways to treat the disease. Current CTE research has primarily focused on how the disease could potentially impact the world of sports. Most notably, CTE has been linked with American football at all levels, though

11008-759: The cause of death, but have also led to discoveries of various diseases such as fetal alcohol syndrome, Legionnaire's disease, and even viral hepatitis. Academic autopsies are performed by students of anatomy for the purpose of study, giving medical students and residents firsthand experience viewing anatomy and pathology. Postmortem examinations require the skill to connect anatomic and clinical pathology together since they involve organ systems and interruptions from ante-mortem and post-mortem. These academic autopsies allow for students to practice and develop skills in pathology and become meticulous in later case examinations. Virtual autopsies are performed using radiographic techniques which can be used in post-mortem examinations for

11136-527: The cause of death. Autopsies are performed for either legal or medical purposes. Autopsies can be performed when any of the following information is desired: For example, a forensic autopsy is carried out when the cause of death may be a criminal matter, while a clinical or academic autopsy is performed to find the medical cause of death and is used in cases of unknown or uncertain death, or for research purposes. Autopsies can be further classified into cases where an external examination suffices, and those where

11264-423: The choices proscribed by the fact-finder's jurisdiction and will detail the evidence on the mechanism of the death. Clinical autopsies serve two major purposes. They are performed to gain more insight into pathological processes and determine what factors contributed to a patient's death. For example, material for infectious disease testing can be collected during an autopsy. Autopsies are also performed to ensure

11392-429: The deceased. Although the Brain Bank contains a variety of brains belonging to many different types of athletes and military personnel, Boston University has made it a priority to study the brains of former American football players. These brains come from players involved in every different level of football and have been at the forefront of some of the most important CTE case studies over the past decade. Dr. Ann McKee

11520-496: The dense extracellular amyloid plaques. Parkinson's disease (PD) is the second most common neurodegenerative disorder. It typically manifests as bradykinesia , rigidity, resting tremor and posture instability. The crude prevalence rate of PD has been reported to range from 15 per 100,000 to 12,500 per 100,000, and the incidence of PD from 15 per 100,000 to 328 per 100,000, with the disease being less common in Asian countries. PD

11648-399: The depths of the sulci. In stage IV CTE, severe p-tau pathology is spread across all areas of the cerebral cortex and temporal lobe. In extreme cases, the tau protein calcarine cortex , which contains the primary visual cortex in the brain. In the study, researchers noted that microscopic signs of p-tau pathology were primarily observed in subjects with Stage III and IV CTE. Two years after

11776-489: The disease. Multiple sclerosis (MS) is a chronic debilitating demyelinating disease of the central nervous system , caused by an autoimmune attack resulting in the progressive loss of myelin sheath on neuronal axons. The resultant decrease in the speed of signal transduction leads to a loss of functionality that includes both cognitive and motor impairment depending on the location of the lesion. The progression of MS occurs due to episodes of increasing inflammation, which

11904-435: The disease. Although CTE remains mysterious and controversial, researchers have observed a link between the disease and the protein called tau , which slowly forms clumps in the brain that kill brain cells. This often results in subjects experiencing depression, anxiety, memory loss, headaches, and sleep disturbances. Boston University's CTE Center was formed as a part of the school's Alzheimer's Disease Center (BU ADC) which

12032-496: The donated brains and brain tissue. These examinations were performed at both the macroscopic and microscopic levels, in order to identify important neuropathological characteristics of CTE, including how the brain deteriorates over time, and the distribution of proteins in brains with CTE. Through microscopic examination, the researchers were able to confirm the role of the tau protein in CTE diagnosis, as well as other proteins that are signs of this degenerative disease. This tau protein

12160-410: The effectors that in turn cleave other proteins resulting in apoptotic initiation. Autophagy is a form of intracellular phagocytosis in which a cell actively consumes damaged organelles or misfolded proteins by encapsulating them into an autophagosome , which fuses with a lysosome to destroy the contents of the autophagosome. Because many neurodegenerative diseases show unusual protein aggregates, it

12288-455: The effort to raise awareness regarding the underfinancing of autopsies. The same sources stated that autopsy rates in Sweden and Finland reach 20 to 30%. In the United States, autopsy rates fell from 17% in 1980 to 14% in 1985 and 11.5% in 1989, although the figures vary notably from county to county. The body is received at a medical examiner's office, municipal mortuary, or hospital in

12416-438: The end of the autopsy. At this stage, the organs are exposed. Usually, the organs are removed in a systematic fashion. Making a decision as to what order the organs are to be removed will depend highly on the case in question. Organs can be removed in several ways: The first is the en masse technique of Letulle whereby all the organs are removed as one large mass. The second is the en bloc method of Ghon. The most popular in

12544-432: The exam may be performed to evaluate any disease or injury that may be present for research or educational purposes. The term necropsy is generally used for non-human animals. Autopsies are usually performed by a specialized medical doctor called a pathologist . Only a small portion of deaths require an autopsy to be performed, under certain circumstances. In most cases, a medical examiner or coroner can determine

12672-418: The first civilizations to practice the removal and examination of the internal organs of humans in the religious practice of mummification . Autopsies that opened the body to determine the cause of death were attested at least in the early third millennium BCE, although they were opposed in many ancient societies where it was believed that the outward disfigurement of dead persons prevented them from entering

12800-506: The formation and expansion of the VA-BU-CLF Brain Bank, McKee is also the director of several other brain banks, all of which are located in Massachusetts. Dr. Chris Nowinski is the co-founder and current CEO of the Concussion Legacy Foundation, an organization dedicated to the awareness and prevention of concussions in every level of sport. Concussions in American football is particularly important to Nowinski as he himself experienced

12928-635: The formation of the bank. The directors of the VA-BU-CLF Brain Bank work with families of former athletes and veterans to create a well-rounded database that researchers can utilize during large CTE case studies. Employees of the Brain Bank collect tissue samples from the central nervous system (brain, eyes, and spinal cord) of deceased athletes, most notably American football professionals, and military veterans. The Bank then stores these samples optimally to ensure proper care and treatment before, during, and after research testing. The Brain Bank directors will also share findings with family members and caregivers of

13056-400: The longer the deceased had gone without a meal before death. The body block that was used earlier to elevate the chest cavity is now used to elevate the head. To examine the brain , an incision is made from behind one ear, over the crown of the head, to a point behind the other ear. When the autopsy is completed, the incision can be neatly sewn up and is not noticed when the head is resting on

13184-526: The loss of the grey matter, and as a result current literature devotes itself to combatting the auto-inflammatory aspect of the disease. While there are several proposed causal links between EBV and the HLA-DRB1*15:01 allele to the onset of MS – they may contribute to the degree of autoimmune attack and the resultant inflammation – they do not determine the onset of MS. Amyotrophic lateral sclerosis (ALS), commonly referred to Lou Gehrig's disease,

13312-714: The mitochondrial membranes, and the mitochondrial permeability transition. Mitochondrial disease leading to neurodegeneration is likely, at least on some level, to involve all of these functions. There is strong evidence that mitochondrial dysfunction and oxidative stress play a causal role in neurodegenerative disease pathogenesis, including in four of the more well known diseases Alzheimer's , Parkinson's , Huntington's , and amyotrophic lateral sclerosis . Neurons are particularly vulnerable to oxidative damage due to their strong metabolic activity associated with high transcription levels, high oxygen consumption, and weak antioxidant defense. The brain metabolizes as much as

13440-566: The most concerning findings have dealt with retired players from the National Football League. As CTE continues to gain notoriety, research focus has shifted to developing a test for diagnosing the disease in a living person. By studying and diagnosing post mortem brains with CTE, researchers at the Boston University CTE Center have been able to map out the disease in the brain, specifically, the various proteins that develop in an affected brain. The most important of these proteins

13568-490: The number of autopsies performed in hospitals has been decreasing every year since 1955. Critics, including pathologist and former JAMA editor George D. Lundberg , have charged that the reduction in autopsies is negatively affecting the care delivered in hospitals, because when mistakes result in death, they are often not investigated and lessons, therefore, remain unlearned. When a person has permitted an autopsy in advance of their death, autopsies may also be carried out for

13696-710: The pivotal CONNECTION trial of patients with mild-to-moderate disease. With CONCERT, the remaining Pfizer and Medivation Phase III trial for Dimebon (latrepirdine) in Alzheimer's disease failed in 2012, effectively ending the development in this indication. In another experiment using a rat model of Alzheimer's disease, it was demonstrated that systemic administration of hypothalamic proline-rich peptide (PRP)-1 offers neuroprotective effects and can prevent neurodegeneration in hippocampus amyloid-beta 25–35. This suggests that there could be therapeutic value to PRP-1. Protein degradation offers therapeutic options both in preventing

13824-492: The possibility of parole. After his death, Hernandez's brain was donated to the VA-BU-CLF Brain Bank, where Boston University researchers, led by Dr. Ann McKee, immediately performed an autopsy on the post-mortem brain. The posthumous examination of the brain showed that Hernandez suffered from stage III CTE, which had previously only been diagnosed in former American football players who were well into their 60s before their deaths. According to Dr. McKee, Hernandez's brain presented

13952-441: The primary cellular sites where SOD1 mutations act are located on astrocytes . Astrocytes then cause the toxic effects on the motor neurons . The specific mechanism of toxicity still needs to be investigated, but the findings are significant because they implicate cells other than neuron cells in neurodegeneration. Batten disease is a rare and fatal recessive neurodegenerative disorder that begins in childhood. Batten disease

14080-686: The proteins that cause the disease works towards manifestation from their early stages in the humans affected by the proteins. Along with being a neurodegenerative disorder, HD has links to problems with neurodevelopment. HD is caused by polyglutamine tract expansion in the huntingtin gene, resulting in the mutant huntingtin. Aggregates of mutant huntingtin form as inclusion bodies in neurons, and may be directly toxic. Additionally, they may damage molecular motors and microtubules to interfere with normal axonal transport , leading to impaired transport of important cargoes such as BDNF . Huntington's disease currently has no effective treatments that would modify

14208-409: The pull of gravity is producing the only blood pressure at this point, related directly to the complete lack of cardiac functionality. However, in certain cases, there is anecdotal evidence that bleeding can be quite profuse, especially in cases of drowning . At this point, shears are used to open the chest cavity. The examiner uses the tool to cut through the ribs on the costal cartilage, to allow

14336-422: The purposes of teaching or medical research. An autopsy is usually performed in cases of sudden death, where a doctor is not able to write a death certificate, or when death is believed to result from an unnatural cause . These examinations are performed under a legal authority ( medical examiner , coroner , or procurator fiscal ) and do not require the consent of relatives of the deceased. The most extreme example

14464-476: The questions pertaining to an autopsy without putting the examiner at risk of biohazardous materials that can be in an individual's body. In 2004 in England and Wales, there were 514,000 deaths, of which 225,500 were referred to the coroner . Of those, 115,800 (22.5% of all deaths) resulted in post-mortem examinations and there were 28,300 inquests , 570 with a jury. The rate of consented (hospital) autopsy in

14592-507: The research process for methods to treat Batten disease. Creutzfeldt–Jakob disease (CJD) is a prion disease that is characterized by rapidly progressive dementia. Misfolded proteins called prions aggregate in brain tissue leading to nerve cell death. Variant Creutzfeldt–Jakob disease (vCJD) is the infectious form that comes from the meat of a cow that was infected with bovine spongiform encephalopathy , also called mad cow disease. The greatest risk factor for neurodegenerative diseases

14720-493: The sciences to answer questions of interest to the legal system. Medical examiners attempt to determine the time of death, the exact cause of death, and what, if anything, preceded the death, such as a struggle. A forensic autopsy may include obtaining biological specimens from the deceased for toxicological testing, including stomach contents. Toxicology tests may reveal the presence of one or more chemical "poisons" (all chemicals, in sufficient quantities , can be classified as

14848-490: The second stab wound Caesar received was the fatal one. Julius Caesar had been stabbed a total of 23 times. By around 150 BCE, ancient Roman legal practice had established clear parameters for autopsies. The greatest ancient anatomist was Galen (CE 129– c.  216 ), whose findings would not be challenged until the Renaissance over a thousand years later. Ibn Tufail has elaborated on autopsy in his treatise called Hayy ibn Yaqzan and Nadia Maftouni , discussing

14976-485: The skull cap is sewed back in place. Then the body may be wrapped in a shroud , and it is common for relatives to not be able to tell the procedure has been done when the body is viewed in a funeral parlor after embalming . An autopsy of stroke may be able to establish the time taken from the onset of cerebral infarction to the time of death. Various microscopic findings are present at times from infarction as follows: Around 3000 BCE, ancient Egyptians were one of

15104-416: The specific region affected, ranging from issues related to movement to the development of dementia. Alzheimer's disease (AD) is a chronic neurodegenerative disease that results in the loss of neurons and synapses in the cerebral cortex and certain subcortical structures, resulting in gross atrophy of the temporal lobe , parietal lobe , and parts of the frontal cortex and cingulate gyrus . It

15232-521: The standard of care at hospitals. Autopsies can yield insight into how patient deaths can be prevented in the future. Within the United Kingdom, clinical autopsies can be carried out only with the consent of the family of the deceased person, as opposed to a medico-legal autopsy instructed by a Coroner (England & Wales) or Procurator Fiscal (Scotland), to which the family cannot object. Over time, autopsies have not only been able to determine

15360-426: The sternum to be removed; this is done so that the heart and lungs can be seen in situ and that the heart – in particular, the pericardial sac  – is not damaged or disturbed from opening. A PM 40 knife is used to remove the sternum from the soft tissue that attaches it to the mediastinum. Now the lungs and the heart are exposed. The sternum is set aside and will eventually be replaced at

15488-528: The subject in an extensive article, believes him to be among the early supporters of autopsy and vivisection . The dissection of human remains for medical or scientific reasons continued to be practiced irregularly after the Romans, for instance by the Arab physicians Avenzoar and Ibn al-Nafis . In Europe they were done with enough regularity to become skilled, as early as 1200, and successful efforts to preserve

15616-550: The synthesis and degradation of irregular proteins. There is also interest in upregulating autophagy to help clear protein aggregates implicated in neurodegeneration. Both of these options involve very complex pathways that we are only beginning to understand. The goal of immunotherapy is to enhance aspects of the immune system. Both active and passive vaccinations have been proposed for Alzheimer's disease and other conditions; however, more research must be done to prove safety and efficacy in humans. A current therapeutic target for

15744-416: The treatment of Alzheimer's disease is the protease β-secretase , which is involved in the amyloidogenic processing pathway that leads to the pathological accumulation of proteins in the brain. When the gene that encodes for amyloid precursor protein (APP) is spliced by α-secretase rather than β-secretase, the toxic protein β amyloid is not produced. Targeted inhibition of β-secretase can potentially prevent

15872-504: The value of any specific therapeutic strategies and drugs when attempting to ameliorate disease severity. An example is the drug Dimebon by Medivation, Inc. In 2009 this drug was in phase III clinical trials for use in Alzheimer's disease, and also phase II clinical trials for use in Huntington's disease. In March 2010, the results of a clinical trial phase III were released; the investigational Alzheimer's disease drug Dimebon failed in

16000-435: The world that focuses on traumatic brain injuries and CTE. In partnership with the VA-BU-CLF Brain Bank, the Boston University CTE Center continues to be the most accomplished CTE research facility in the world, as the Center houses 70% of global CTE cases. The goal of the Boston University CTE Center is to collect and study post-mortem brains to better understand the long-term diseases associated with head trauma. Specifically,

16128-486: Was established in 1996. As the prominence of long-term brain injuries continued to grow in the early 2000s, the CTE Center collaborated with the United States Department of Veteran Affairs and the Concussion Legacy Foundation to form the VA-BU-CLF Brain Bank. This Brain Bank was officially formed in 2008, and acts as a subset of the Boston University School of Medicine. A brain bank is designed to act as

16256-405: Was neurodegeneration or suicide. Each brain was evaluated and CTE p-tau pathology for the brains were classified into a stage of CTE. The study showed that of the 202 evaluated brains, CTE was neuropathologically diagnosed in 177 (87%), including 110 of 111 former NFL players (99%). In all cases of CTE, clusters of the tau protein were found in the cerebral cortex, consistent with earlier studies from

16384-488: Was present in each brain that was diagnosed with CTE, demonstrating its role in the development of the disease. From these post-mortem tests, researchers were able to detail the characteristics of the various stages of CTE. In the study, the Boston University researchers grouped the subjects into four distinct stages of CTE, with each stage increasing in severity. In stage I CTE, p-tau pathology can be observed in

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