Autism BrainNet
A Collaboration Between Medical Examiners, Pathologists, Researchers, and
Families to Advance the Understanding and Treatment of Autism Spectrum
Disorder
Matthew P. Anderson, MD, PhD; Reade Quinton, MD; Karen Kelly, MD; Andrew Falzon, MD; Alycia Halladay, PhD;
Cynthia M. Schumann, PhD; Patrick R. Hof, MD; Carol A. Tamminga, MD; Carolyn Komich Hare, MS; David G. Amaral, PhD
 Context.—Autism spectrum disorder is a neurodevelop- are located in Oxford, England and Montreal, Quebec,
mental condition that affects over 1% of the population Canada.
worldwide. Developing effective preventions and treat- Data Sources.—Pubmed, Autism BrainNet.
ments for autism will depend on understanding the Conclusions.—Because the death of autistic individuals
neuropathology of the disorder. While evidence from is often because of an accident, drowning, suicide, or
magnetic resonance imaging indicates altered develop- sudden unexpected death in epilepsy, they often are seen
ment of the autistic brain, it lacks the resolution needed to in a medical examiner’s or coroner’s office. Yet, autism is
identify the cellular and molecular underpinnings of the rarely considered when evaluating the cause of death.
disorder. Postmortem studies of human brain tissue Advances in our understanding of chronic traumatic
currently represent the only viable option to pursuing encephalopathy have occurred because medical examiners
these critical studies. Historically, the availability of autism and neuropathologists questioned whether a pathologic
brain tissue has been extremely limited. change might exist in individuals who played contact
Objective.—To overcome this limitation, Autism Brain- sports and later developed severe behavioral problems.
Net, funded by the Simons Foundation, was formed as a This article highlights the potential for equally significant
network of brain collection sites that work in a coordinat- breakthroughs in autism arising from the proactive efforts
ed fashion to develop a library of human postmortem brain of medical examiners, pathologists, and coroners in
tissues for distribution to researchers worldwide. Autism partnership with Autism BrainNet.
BrainNet has collection sites (or Nodes) in California, (Arch Pathol Lab Med. 2021;145:494–501; doi: 10.5858/
Texas, and Massachusetts; affiliated, international Nodes arpa.2020-0164-RA)
Autism Spectrum Disorder (ASD) affects 1 of 59 people inthe United States, and likely worldwide, with 4 times
Accepted for publication June 18, 2020. as many males diagnosed compared with females.1 Accord-
Published online September 22, 2020. ing to the Diagnostic and Statistical Manual, the core
From the Departments of Neurology and Pathology, Beth Israel diagnostic symptoms of autism are as follows: (1) persis-
Deaconess Medical Center, Harvard Medical School, Boston,
Massachusetts (Anderson); Department of Laboratory Medicine and tently impaired social communication and interaction, and
Pathology, Mayo Clinic, Rochester, Minnesota (Quinton); Depart- (2) restricted, repetitive patterns of behavior, interests, or
ment of Pathology and Laboratory Medicine, Brody School of activities.
Medicine at East Carolina University Greenville, North Carolina These symptoms arise early in development and may
(Kelly); Office of the Chief State Medical Examiner, Trenton, New manifest as problems with social conversation, understand-
Jersey (Falzon); Autism Science Foundation, New York, New York
(Halladay); Department of Pharmacology and Toxicology, Rutgers ing nuances of language, or engaging with peers in social
University, Piscataway, New Jersey (Halladay); The MIND Institute, activities. Challenges in nonverbal communication are also
University of California at Davis, Sacramento (Schumann and seen including problems in the use or interpretation of body
Amaral); Nash Family Department of Neuroscience, Friedman Brain language (gesturing) and facial expressions. Restricted and
Institute, and Seaver Autism Center for Research and Treatment, repetitive patterns of behavior can include self-stimulatory
Icahn School of Medicine at Mount Sinai, New York, New York
(Hof); Department of Psychiatry, University of Texas Southwestern (stimming) behaviors, fixated interest on objects (eg, toys,
Medical Center, Dallas (Tamminga); and Autism BrainNet, New cars), insistence on sameness, difficulty with changing
York, New York (Hare). routine, and hypersensitivity or hyposensitivity to light or
The authors have no relevant financial interest in the products or sound.2
companies described in this article. Typically, the diagnosis can be made by 24 months of age,
Corresponding author: Matthew P. Anderson, MD, PhD, Depart- 3,4
ment of Pathology, Beth Israel Deaconess Medical Center, 330 but sometimes not until 36 months or later, although
Brookl ine Ave, E/CLS-645, Boston, MA 02215 (emai l : earlier detection and diagnosis is sought for early treatment
Matthew_Anderson@bidmc.harvard.edu). intervention. There is a wide range of symptom severities.
494 Arch Pathol Lab Med—Vol 145, April 2021 Brain Banking for Autism—Anderson et al
However, the autism diagnosis is also dependent on cases of ASD.28–32 There have also been reports of reduced
significant clinical impairment, such that symptoms interfere neuronal size and local number, particularly of pyramidal
with daily functions. Of note, individuals with autism often neurons, in several neocortical areas, including the fusiform
have comorbid medical, neurologic, and psychiatric symp- face area, the anterior insula, Broca’s area, the posteroin-
toms, including seizures sometimes resulting in sudden ferior occipital gyrus, and the anterior cingulate cortex, in
unexpected death in epilepsy,5 gastrointestinal symptoms,6 cases of idiopathic autism.13,33–36 This has also been
anxiety, depression sometimes resulting in suicide, and observed to some degree in cases of ASD associated with
sleep problems.7 Individuals with autism may also demon- maternal 15q11-13 duplication, dup15q syndrome.33 Of
strate varying deficits in language and cognitive ability, note, postmortem brains from dup15q syndrome (a
ranging from profound disability to savant skills.8 Previous relatively frequent and strongly penetrant genetic cause of
to the most recent version of the Diagnostic and Statistical ASD37–39) also share many of the changes in gene expression
Manual, there were different subtypes of autism, including and DNA methylation found in idiopathic ASD.40,41
Asperger syndrome and Pervasive Developmental Disorder Regions of the brain associated with social and emotional
Not Otherwise Specified. In 2013, these subtypes were cognition, such as the amygdala and prefrontal cortices, are
collapsed into 1 diagnosis ‘‘Autism Spectrum Disorder’’ also implicated in the neuropathology of ASD. A number of
(ASD).8 magnetic resonance imaging studies find these brain regions
Because a diagnosis of ASD requires specialized clinical are, in general, larger in children with ASD and do not
training, many pediatricians and pediatric and adult undergo the same growth trajectory that occurs in neuro-
typical development.42–44neurologists and psychiatrists taking care of these individ- Although magnetic resonance
uals for other conditions (eg, epilepsy or depression) will imaging studies provide a macroscopic view of when and
often use more generic labels, such as developmental delay where the brain may be developing differently in people
or neurodevelopmental disorder. It is therefore important to with ASD, postmortem brain tissue is required to under-
be aware of alternative labels when considering whether a stand the underlying cellular and molecular mechanisms.
death might have arisen in connection with a case of autism. For example, a recent study of 52 human postmortem brains
There is a higher mortality rate in autism compared with found that the enlarged amygdala in children with ASD may
those without this diagnosis (further details below), and the be because of an excess number of neurons.
12 In contrast,
causes of death differ based on sex and the presence or adults with ASD have fewer neurons, spines, and oligo-
absence of intellectual disability.9 Postmortem diagnosis of dendrocytes in the amygdala indicating potential degener-
12,45,46
autism through interview of a parent or other caregiver has ative processes. In addition, functional magnetic
been validated10 and is now in common use by Autism resonance imaging studies have pointed to impairment in
BrainNet. face recognition and decreased activity in the fusiform face
area in patients with ASD, which correlates to findings of
WHAT IS KNOWN ABOUT THE NEUROPATHOLOGY OF abnormal pyramidal neuron numbers and volumes, specif-
ASD? ically in this cortical region.
36,47 In addition, empathy deficits
in ASD patients have been correlated to dysfunction of the
As realized now for other behavioral disorders, such as anteroinferior insular cortex, a region in which neuron type-
chronic traumatic encephalopathy,11 the goal of eventually specific alterations are known to occur in ASD.35,48
achieving a comprehensive understanding of the neuropa- Approximately 10% to 15% of autism cases carry genetic
thology and neurobiology of autism will require contribu- defects that are considered to play a major causal role in the
tions of the frontline efforts of medical examiners and behavioral disorder. The rapidly increasing number of
pathologists who see many of the autism postmortem cases. autism-associated genetic defects include the following: (1)
The neuropathology of autism spectrum disorder is a rapidly large cytogenetic abnormalities, such as extranumerary
evolving area of research.12–14 The first substantial papers isodicentric chromosome 15q (idic[15]); (2) minute deletions
using postmortem brain tissue from individuals with ASD or duplications of regions of the genome called copy
were published in the mid-1980s15; however, the paucity of number variations; and (3) single nucleotide mutations
available brains has slowed progress.16 Much of our within the exome or coding sequences of specific genes.49
knowledge since has come from magnetic resonance Genetic analysis of the autism postmortem brain cases has
imaging studies (reviewed in Ref. 17). Recent studies reveal already begun and is ongoing.50 Of note, no single genetic
increased extra-axial cerebrospinal fluid volumes18,19 in defect accounts for more than 1% of the autism cases. The
children at risk for autism. A subset (~15%) of individuals large number of genetic changes in ASD has suggested to
with ASD have enlarged heads (macrocephaly) and brains some that the use of behavioral measurements to diagnose
(megalencephaly),20,21 including ASD, because of some rare autism may capture a heterogenous group of neurodevel-
genetic disorders that magnify PI3K-AKT-mTOR signaling opmental disorders.
pathway, such as phosphatase and tensin homolog (PTEN) Despite this clear genetic heterogeneity, there is some
heterozygosity22 and heterozygous mutations of the gene evidence of convergence of these genetic defects into
regulatory chromodomain helicase DNA binding protein 8 specific molecular pathways. These pathways include those
(CHD8).23 Studies have also reported defects in brain underlying gene regulation and chromatin modification (eg,
development that implicate in utero insults to the fetal CHD8) and, more directly, the pathways that determine
brain. Cortical dysplasia is found in cases of idiopathic how neuronal circuits of the brain function, including genes
ASD24–26 and in tuberous sclerosis with TSC1 and TSC2 encoding synaptic proteins (eg, neurexin, glutamate recep-
gene mutations where the dysplasia correlates with the tor delta subunit, or SHANK family members).
severity of autistic traits.27 Decreased numbers of cerebellar Beyond these rarer genetic forms of autism, there is
Purkinje neurons (with relative preservation of the inferior building evidence of a neuroimmune form of autism based
olive but also basket cells) suggests an early but post- on the findings of ongoing neuroinflammation in a majority
developmental mechanism found in a subset of idiopathic of autism postmortem brains.51 These discoveries were
Arch Pathol Lab Med—Vol 145, April 2021 Brain Banking for Autism—Anderson et al 495
made possible using the limited human autism and in preparation for writing this article, we reviewed the
matching control postmortem brain tissues collected, in database held by the Office of the State Medical Examiner in
part, from medical examiners and pathology departments New Jersey and found that of 593 840 reported deaths
across the country. This neuroinflammatory phenotype between 1989 and 2017, only 22 cases had ‘‘Autism’’
within the brain is reflected in increased levels of cytokine included in the cause of death. Of these 22 cases, the
and chemokine proteins and reactive astroglial and microg- majority were white (16 cases) and male (21 cases), with an
lial transcripts.51–54 Recent studies using advanced single- age range of 13 to 70 years (mean age of 34.5 years).
cell sequencing techniques in postmortem autism brain Included in the cause of death of these individuals were
specimens have revealed transcriptional changes that are conditions that are seen at a higher rate in people with a
most dramatic in upper cortical layer excitatory neurons diagnosis of ASD, such as seizures and drowning. In other
along with evidence of an activated microglial response.55 A cases, autism was simply added as a contributory cause
significant number of the postmortem autism donors have without the condition actually leading to the person’s
epilepsy and have died of sudden unexpected death in demise, as was the case of a 70-year old whose proximate
epilepsy. Sudden unexpected death in epilepsy is a fatal cause of death was listed as ‘‘Stroke due to atherosclerosis’’
complication of epilepsy defined as the sudden and (unpublished observations). When completing the death
unexpected, nontraumatic and nondrowning death of a certificate, the physician should consider any potentially
person with epilepsy, without anatomic or toxicologic lethal conditions of increased risk in a case of autism (see
causes of death detected upon completion of the postmor- below) in order to accurately complete the death certifica-
tem examination. One potential explanation for the high tion for these cases.
incidence of an inflammatory state in the autism brain is Medical examiners face the challenge of establishing a
seizures, yet seizures do not correlate with the changes direct link between autism and the underlying cause of
identified by single-cell sequencing55 or the T-cell infiltrates death. In general, physicians would not have an issue
recently discovered in the ASD postmortem brain (see adding autism as a contributory factor to the cause of death
below).56 when, for example, it is classified as ‘‘Sudden Unexpected
The driver of this inflammatory state present in a majority Death in Epilepsy’’ given the strong correlation between the
of autism brain remains undefined, but recent studies 2 conditions. Arguably, even the deficits of ASD (eg, poor
suggest a subset of autism cases may be caused by social skills, insensitivity to pain) can lead to diagnostic
autoimmune disease. Approximately 5% to 10% of cases delays and jeopardize optimal health care, exacerbating
of autism have been associated with maternal antibodies potentially treatable conditions, such as pneumonia that
directed at the fetal brain57,58 and a larger proportion of could end with a fatal outcome. It is the position of this
autism cases may have self-directed antibodies57,59 impli- group that in light of the increased mortality rate in patients
cating the humoral immune system (B cells). While with ASD, a careful case review should be conducted when
performing neuropathologic examinations of the postmor- completing the death certificate in order to identify any
tem brains from individuals with autism collected into association between the cause of death and autism. The
Autism BrainNet, increased numbers of perivascular CD8- main causes of premature death in ASD includes the
rich T-lymphocyte cuffs were observed in approximately following.
65% of autism cases relative to control cases (Figure 1, A–L). Epilepsy
In addition, a unique pathology, astrocyte membranous
debris, was found in the Virchow-Robin perivascular and Epilepsy co-exists with autism in 20% of children and is
particularly frequent in those with intellectual disabilities. A
subarachnoid cerebrospinal fluid spaces, which resemble
strong correlation exists between deaths associated with
the blebs generated when cytotoxic T-cells attack tumor
56 epilepsy and ASD.
65 Recent studies have demonstrated
cells (Figure 2, A–O). Interestingly, the quantity of these
þ multiple genomic variants that may account for the co-GFAP astrocyte blebs (Figure 2, D–I) correlated to the
existence of these conditions.66 Increased awareness and
number of lymphocytes across the autism cases (Figure 3).
further research in this area may lead to the development of
While still under investigation, these findings suggest the
novel therapeutic interventions to reduce the high incidence
possibility that a lymphocyte-based adaptive T-cell immune of premature death related to the seizures in ASD. Seizures
response might drive the inflammatory state of the brain in account for 7% to 30% of deaths in individuals with ASD,
autism. These exciting new findings represent possible new including sudden unexpected death in epilepsy, intractable
therapeutic targets that are not yet a part of the standard seizures, and cardiac/respiratory arrest as a consequence of
treatment for ASD and could positively impact the lives of seizures.62,67,68
many individuals and their families. Further studies of the
human postmortem brain in ASD are essential to justify and Suicide
motivate the expensive clinical trials that will need to be Depression is more commonly diagnosed in persons with
performed to advance the standard of treatment in autism ASD who have preserved language fluency and average or
based on these new and exciting findings. above intellectual functioning. Persons with this particular
ASD profile often present with co-existing psychiatric
WHAT IS KNOWN ABOUT THE CAUSES OF DEATH IN conditions.69 Importantly, individuals (children and adults;
ASD? females . males) with autism have a much higher incidence
A 2016 study in Sweden on the premature mortality in of suicidal ideation and attempts as compared with the
ASD showed that individuals with this diagnosis have a 2.5- general population.9,70–72
fold higher risk of premature death as compared with the
general population.9 Other studies have confirmed this Accidental Deaths/Wandering/Elopement
increased standardized mortality ratio among individuals Accidental deaths including drowning and suffocation are
with ASD in different population groups.60–64 Interestingly, more frequent in ASD as compared with the general
496 Arch Pathol Lab Med—Vol 145, April 2021 Brain Banking for Autism—Anderson et al
Figure 1. Expanded lymphocytic cuffs were found in approximately 65% of autism spectrum disorder cases. Representative images of blood vessels
in the brain parenchyma of 2 control patients (A–D) and 4 patients carrying an autism diagnosis (E–H) (including genetic conditions PTEN
heterozygous mutations of phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase, PTEN [I and J], and an
extra Y chromosome, XYY [K and L]) show increased abundance of perivascular lymphocytes in the autism cases. H&Eþ LFB, hematoxylin and eosin/
luxol fast blue (myelin) stain. All scale bars represent 40 lm. All available H&E þ LFB–stained slides were reviewed with a standard bright field
microscope, and photographs were taken using a360 objective (3600 total magnification). Adapted from Distasio et al. Annals of Neurology, 2019
with permission by John Wiley & Sons, Inc.
Figure 2. Astrocyte blebs form from the glia limitans at the cerebrospinal fluid–brain barrier in autism spectrum disorder. Left, Round and uniformly
eosinophilic membranous blebs of varying sizes were identified in the perivascular Virchow-Robin spaces of autism brains (A–C). H&E þ LFB,
hematoxylin and eosin/luxol fast blue (myelin) stain (A–C). Middle, glial fibrillary acidic protein (GFAP) immunohistochemistry with high
magnification view of astrocyte foot processes (white arrows) extending to glia limitans where blebs are forming (D–I). Right, S100B, astrocyte
marker immunohistochemistry (J–L). Right, Aldehyde Dehydrogenase 1 Family Member L1 (ALDH1L1), a cytosolic 10-formyltetrahydrofolate
dehydrogenase, immunohistochemistry labeling astrocytes (M–O). All scale bars represent 40 lm. Photographed using a340 objective (3400 total
magnification). Adapted from Distasio et al. Annals of Neurology, 2019 with permission by John Wiley & Sons, Inc.
Arch Pathol Lab Med—Vol 145, April 2021 Brain Banking for Autism—Anderson et al 497
associated co-morbidities/risks to accurately capture this
information.
WHAT IS AUTISM BRAINNET AND WHY WAS IT
ESTABLISHED?
Researchers studying other clinical disorders such as
Parkinson disease, Alzheimer disease, and schizophrenia
have demonstrated substantial success in collecting brain
donations with a confederated model of regional collection
sites distributed across the country. The Stanley Brain
Collection, focused on schizophrenia and bipolar disorder,
was an inspiration for Autism BrainNet. When the Stanley
Brain Collection began in 1994, there was a severe shortage
of brain tissue available for research on these major
psychiatric diseases. In a decade and a half, the Stanley
Brain Collection has successfully collected more than 600
brains into their network, resulting in research publications
employing a wide range of methodologies and examining a
diverse array of brain regions.77
For Autism BrainNet, a plan was drafted in 2009 that
proposed the implementation of a confederated network
model for the optimal acquisition, preparation, and distri-
bution of postmortem brains to support autism research. In
Figure 3. The quantity of perivascular astrocyte debris correlates to
perivascular lymphocytes in autism spectrum disorder. A plot of short, this model was composed of a series of university-
perivascular GFAPþ debris against perivascular lymphocyte counts based collection sites around the country. A key element of
(top 16 vessels) for each case shows the correlation between the model was that although brain tissue would be collected
astrocyte-derived debris and lymphocyte numbers. **P , .001 for linear regionally at several sites, all acquired tissue would
regression; the rank-order correlation has a Kendall’s tau of 0.51 (P ¼ contribute to a general pool for use by the autism research
.01). Adapted from Distasio et al. Annals of Neurology, 2019 with
permission by John Wiley & Sons, Inc. community. The rationale for having several regional
collection sites was 2-fold. First, it was thought that families
would be more inclined to make a donation to an institution
population.61,73 Poor social communication is thought to that had local name recognition; second, collecting cases
predispose ASD individuals to an increased risk of locally could reduce the interval from death to brain
accidental death. Roughly half of children with ASD attempt processing.
to elope from their safe environment at a rate nearly 4 times To insure standardized regulatory management across all
higher than their unaffected siblings.74–76 Accidental drown- Nodes, Autism BrainNet engaged the services of Western
ing accounts for 70% to 90% of total US deaths reported in institutional review board to provide in-depth expertise and
children with ASD ages 14 and younger subsequent to capacity for multisite coordination. Before launching these
wandering/elopement.73,74 More than one-third of ASD operations, the Western institutional review board conduct-
children who wander/elope are never or rarely able to ed an initial review of Autism BrainNet’s standard operating
communicate their name, address, or phone number. Two- procedures, including clinical processes (consenting and
thirds of parents of elopers reported that their missing postmortem characterization of donated brain tissue). Upon
children had a ‘‘close call’’ with a traffic injury or satisfying the Western institutional review board’s require-
drowning.74 ments, effective June 19th, 2014, the Western institutional
Other review board provided a certificate of approval for Autism
BrainNet’s national consent for postmortem tissue dona-
Excluding seizures, suicides, and accidents, the cause of tion, and consent for donor family clinical documentation,
death in the remaining ASD group mirrors the heteroge- clinical questionnaires, and protocol. Once the Node sites
nous medical conditions seen in the general population, were selected and institutional review board oversight was
including cardiac and cancer-related deaths. established, Autism BrainNet was formally launched at the
Given the wide symptomatic variation of ASD, the International Meeting for Autism Research in May of 2014.
presence of co-morbidities, and the possible side effects of The overall structure of Autism BrainNet is illustrated in
medications, determining the exact cause of death in ASD Figure 4.
can be a challenge for the physician completing the death Each of the nodes is staffed with personnel who are highly
certificate. In the forensic setting, medical examiners and trained in the preparation and storage of donated brains.
coroners may not be aware of the diagnosis of ASD. Scene Using standard operating procedures that are consistent
investigators should question the family about the possibil- across all nodes, these staff prepare 1 hemisphere as
ity of autism in cases with death related to the mechanisms unfixed, fresh-frozen coronal slabs while the contralateral
listed above. The authors suspect that many cases of ASD hemisphere is fixed and is used for neuroanatomic studies
have been missed in the past because of the lack of and a clinical neuropathology report when required. The
awareness of these presenting features. Because death fixed half is alternated or directed to the side with clinical,
certificates are the principal source of statistical data, it radiologic, or gross evidence of brain disease. A number of
would be beneficial if physicians (including medical meetings took place, with the assistance of several
examiners) familiarized themselves with autism and any knowledgeable consultants, to establish the standard
498 Arch Pathol Lab Med—Vol 145, April 2021 Brain Banking for Autism—Anderson et al
Figure 4. Overall organizational structure of Autism BrainNet (ABN).
operating procedures for preparation of the brain tissue. brain will be sent. Any medical examiner, pathologist,
This is an evolving process, with the goal of establishing diener, or scene investigator can support Autism BrainNet
procedures that will allow distribution of samples from each by emailing or faxing a daily list of cases for review
brain to as many researchers as possible. By collating the (following Health Insurance Portability and Accountability
experimental results (eg, genetics, neuropathology, immu- Act regulations), or by calling the hotline regarding a
nology, neurobiology) from each case and individual specific donation. It is very important to watch for both
samples into a central data repository, it is anticipated that autism (any age) and control cases (,50 years of age); the
the ASD cases can be subclassified into more uniform sets, collection of autism cases is growing while the number of
possibly with shared etiologic mechanisms, enriching the control cases is beginning to fall behind. The National
value of each donation over time. Association of Medical Examiners supports the efforts of
individual medical examiners by providing Autism Brain-
Successful Collaborations with Medical Examiners Offices Net’s contact information on its website.
and Pathology Autopsy Services The benefits of partnering with Autism BrainNet include
Over the past several years, Autism BrainNet has the following: (1) reimbursement for time, materials, and
developed successful partnerships with medical examiner other costs associated with brain recovery; (2) a free gross
offices around the country. Each of these partnerships is examination or full clinical neuropathology report by an
uniquely configured based upon the demands, state statutes, expert clinical neuropathologist at Harvard Medical School,
culture, and interests of the physicians and staff at each including gross and microscopic examinations and clinical
medical examiner’s office. For example, in 1 medical diagnoses with references, includes standard hematoxylin
examiner’s office, Autism BrainNet provides an embedded and eosin and luxol fast blue myelin stain (demyelinating
diener who conducts brain removal after identifying and diseases), as well as other special and immunohistochemical
consenting potential donors. Another medical examiner’s stains for infectious organisms (bacteria, fungus, spiro-
office designates an Autism BrainNet supported staff person chetes, and specific central nervous system viruses), T-
to review daily field investigation reports to identify lymphocytes and B-lymphocytes (autoimmune or viral
potential donors; this individual then conducts the consent encephalitis), reactive astrogliosis and microgliosis, neo-
when appropriate. A third example involves a medical plasms, b-amyloid and tau proteins (typical of chronic
examiner who alerts Autism BrainNet about potential traumatic encephalopathy, chronic traumatic encephalopa-
donors by calling the 24/7 donor hotline. In this example, thy ,and other neurodegenerative diseases), and neuronal
Autism BrainNet clinical staff do the consenting and the abnormalities (cortical dysplasia or heterotopias, ischemic/
medical examiner procures the brain and uses packaging hypoxic injuries or strokes, changes typical of mesial
sent to the medical examiner’s office and courier services temporal lobe epilepsy). Molecular diagnostic tests are not
arranged by the nearest Node tissue coordinator where the routinely performed during the neuropathology workup for
Arch Pathol Lab Med—Vol 145, April 2021 Brain Banking for Autism—Anderson et al 499
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