Brain bank of the Brazilian aging brain study group—a milestone

Cell Tissue Banking (2007) 8:151–162
DOI 10.1007/s10561-006-9022-z
Brain bank of the Brazilian aging brain study group—a
milestone reached and more than 1,600 collected brains
Lea Tenenholz Grinberg Æ Renata Eloah de Lucena Ferretti Æ
José Marcelo Farfel Æ Renata Leite Æ Carlos Augusto Pasqualucci Æ
Sérgio Rosemberg Æ Ricardo Nitrini Æ Paulo Hilário Nascimento Saldiva Æ
Wilson Jacob Filho Æ Brazilian Aging Brain Study Group
Received: 16 April 2006 / Accepted: 5 July 2006 / Published online: 31 October 2006
Springer Science+Business Media B.V. 2006
Abstract
Introduction Brain banking remains a necessity
for the study of aging brain processes and related
neurodegenerative diseases. In the present
paper, we report the methods applied at and the
first results of the Brain Bank of the Brazilian
Aging Brain Study Group (BBBABSG) which
has two main aims: (1) To collect a large number
of brains of elderly comprising non-demented
subjects and a large spectrum of pathologies
related to aging brain processes, (2) To provide
quality material to a multidisciplinar research
network unraveling multiple aspects of aging
brain processes and related neurodegenerative
diseases.
Methods The subjects are selected from the
Sao Paulo Autopsy Service. Brain parts are
L. T. Grinberg (&) Æ R. E. de Lucena Ferretti Æ
R. Leite Æ C. A. Pasqualucci Æ S. Rosemberg Æ
P. H. N. Saldiva
Department of Pathology, University of Sao Paulo
Medical School, Avenida Dr. Arnaldo, 455 1st floor,
room 1351, Sao Paulo, SP 01246-903, Brazil
e-mail: [email protected]
J. M. Farfel Æ W. Jacob Filho
Division of Geriatrics, University of Sao Paulo
Medical School, Sao Paulo, SP, Brazil
R. Nitrini
Department of Neurology, University of Sao Paulo
Medical School, Sao Paulo, SP, Brazil
frozen and fixated. CSF, carotids, kidney, heart
and blood are also collected and DNA is
extracted. The neuropathological examinations
are carried out based on accepted criteria, using
immunohistochemistry. Functional status are assessed through a collateral source based on a
clinical protocol. Protocols are approved by the
local ethics committee and a written informed
consent form is obtained.
Results During the first 21 months, 1,602 samples were collected and were classified by Clinical Dementia Rating as CDR0: 65.7%;
CDR0.5:12.6%, CDR1:8.2%, CDR2:5.4%, and
CDR3:8.1%. On average, the cost for the processing each case stood at US$400. To date, 14
laboratories have been benefited by the
BBBABSG.
Conclusion The high percentage of nondemented subjects and the ethnic diversity of
this series may be significantly contributive toward aging brain processes and related neurodegenerative diseases understanding since
BBBABSG outcomes may provide investigators
the answers to some additional questions.
Keywords Aging Æ Alzheimer’s disease Æ Brain
banking Æ Dementia Æ Geriatrics Æ
Neurodegenerative diseases Æ Neurology Æ
Neuropathology
123
152
Abbreviations
BBASG
Brazilian Brain Aging Study Group
BBBABSG Brain Bank of the Brazilian Aging
Brain Study Group
CNS
Central nervous system
CS
Collateral source
ICF
Informed consent form
NOK
Next-of-kin
PMI
Postmortem interval
SPAS
Sao Paulo autopsy service
USPMS
University of Sao Paulo Medical
School
Cell Tissue Banking (2007) 8:151–162
In the present paper, we report the methods
applied at and the first results of the Brain Bank
of the Brazilian Aging Brain Study Group
(BBBABSG). This brain bank has two main aims:
(1)
(2)
Introduction
The world’s elderly population is expected to increase four times from 2000 to 2050 (UN Population Division 2000). This will inevitably be
followed by a great increase in the prevalence of
related neurodegenerative diseases particularly, in
developing countries (Ferri et al. 2005; Herrera
et al. 2002). Animal models on age-related human
diseases mimic the complex pathogenic interactions within the highly evolved human CNS only in
a limited manner. Therefore, in order to elucidate
environmental, genetic, and endogenous processes
in human aging and in neurodegenerative diseases
investigation on human brain tissue is precondition. For that reason, brain banks gained an
important function during the last years as autopsy
is the only practical way in which human brain
tissue can be assessed (Cruz-Sanchez and Tolosa
1993). However, considering the high complexity
of the brain anatomy and function, a proper brain
bank have to be a scientific facility, conducted by
multiprofessional experts who assess the subject’s
cognitive and functional status, and where the
material is processed following high standard protocols (Love 2004).
Although there are many successful brain
banks (Hulette 2003; Orr et al. 2005), the majority of them are affected by the inhered consequences of the worldwide dramatic decreased
autopsy rates of past decades resulting in: a low
number of enrolled subjects, mainly the non-demented cases; a lack of objective information
about comorbidities in brain-only autopsies; and
long postmortem interval (PMI).
123
To perform a large number of autopsies of
elderly individuals; the donors come to autopsy through a general autopsy service,
followed by specific dissection protocols.
The collected cases should comprise a large
number of non-demented subjects and a vast
spectrum of pathologies related to aging
brain processes.
To provide high quality material to a multidisciplinar research network unraveling
multiple aspects of aging brain processes and
related neurodegenerative diseases.
Methods
Core board
The BBBABSG has been created in September
2003 by the core board of the Brazilian Brain
Aging Study Group (BBASG). BBASG is composed by a group of different specialists from the
University of Sao Paulo Medical School
(USPMS) (Fig. 1).
Quality control
The first months were fully dedicated to the
study design and pilot tests. Clinical scales and
questionnaires were discussed and tested in the
USPMS’ Cognitive Study Center, a multidisciplinar research facility. Meanwhile, both the
pathological protocol and the electronic database
were formatted based on previous successful
experiences (Cruz-Sanchez and Tolosa 1993).
In 2004, following a study involving all the
clinical and pathological steps, BBBABSG began
to work under full power.
In order to keep the BBBABSG up-to-date
and improve its quality, communication with
other brain banks like the Netherlands Brain
Bank and the Washington University in St. Louis
Brain Bank is carefully maintained, including
on-site visits and fellowships.
Cell Tissue Banking (2007) 8:151–162
153
Fig. 1 Brazilian Brain
Aging Study Group’s
board members
Ethical issues
BBBABSG’s procedures are approved by the
Ethical Board of USPMS and by the Brazilian
Federal Health Department. The ethical principles follow Brazilian requirements (1996), which
are based on international standards, such as The
Belmont Report (National Commission for the
Protection of Human Subjects of Biomedical and
Behavioral Research 1978) and The Helsinki
Declaration (1964). A voluntary Informed Consent Form (ICF) is obtained by the interviewer
and must be signed by each next-of-kin (NOK)
before any procedure. The ICF details research
procedures (including image, molecular and genetic studies), purposes, risks and benefits, as well
as a statement offering the NOK the opportunity
to ask questions and to withdraw at any time from
the study. If any of the procedures is refused by
the NOK, the case is not banked.
All the material used for any purpose is
anonymous and the specimens are coded by
number. However, specimen identification can be
retrieved in case of legal or public health
requirements, according to Brazilian regulations.
Source of subjects
In Sao Paulo, autopsies are compulsory for those
who have died in the metropolitan areas with no
established cause of death, at no charge to the
family. The Sao Paulo Autopsy Service (SPAS) is
the site of all autopsies of natural deaths from this
city of 11 million people. SPAS has functioned
24 h a day since 1931 and is located within
USPMS, adjacent to the BBBABSG’s facilities.
All autopsies complete and documented, are
performed by a medically qualified pathologist
assisted by nationally certified technicians.
Brains are obtained at autopsy of subjects aged
50 years or older and sourced from the SPAS.
BBBABSG’s procedures
Only the centralized Municipal Autopsy Service
is allowed to transport deceased bodies. The time
frame is 2–6 h from the hospital or home to SPAS
resulting in a short PMI mean of 10.4 h (4–20 h).
BBBABSG is structured into five areas
(Fig. 2).
Reception, selection and informed consent
Reception and selection (Fig. 3)
Subjects are enrolled from Monday through
Friday, between 8 and 18 h. Two rotating teams
of two experienced gerontologists each are on
shift at the SPAS during this period. Deceased
123
154
Cell Tissue Banking (2007) 8:151–162
RECEPTION, SELECTION AND
INFORMED CONSENT
B
B
B
A
B
S
G
CLINICAL AND FUNTIONAL ASSESSMENT
Inclusion criteria:
(i)
Subjects aged 50 years old and older.
NEUROPATHOLOGICAL PROCEDURES
Exclusion criteria:
DNA BANK
ELETRONIC DATABASE
Fig. 2 Brain Bank of the Brazilian Aging Brain Study
Group structure. Sao Paulo, 2006
information is received in SPAS before the
corpse’s arrival, allowing a subject pre-selection.
The NOK must come personally to SPAS in order
to give release of the body. Upon arrival, the
NOK waits around 3 h for autopsy procedures
and the release of documents. If the consent is
granted and a satisfactory collateral source (CS)
is on-site, the clinical and functional interview is
conducted in a private room. The NOK and the
CS are not necessarily the same person.
During the interview, the gerontologist judges
whether there is enough information available to
rate the subject, as well as whether the CS is
reliable. The subject is excluded from the study if
any of these criteria is not fulfilled.
Fig. 3 Flowchart of the
Brain Bank of the
Brazilian Aging Brain
Study Group’s
procedures—2006
123
Selection criteria
(i)
Subjects with macroscopically detectable
acute brain infarctions, hemorrhages or
trauma, since an immediate examination is
required for filling the death certificate.
(ii) Subjects with severe chronic conditions that
might damage cognitive function prior to
death by interfering in brain homeostasis.
These conditions include severe heart failure, chronic kidney failure and brain
metastasis.
(iii) Subjects without reliable CS to provide
enough information or to appropriately
answer the clinical and functional interview.
Eligible CS are expected to have at least
close weekly contact with the diseased
subject during the last 6 months.
(iv) Subjects with indication of acidosis due to
severe agonal status (CSF pH < 6.5), which
makes the tissue incompatible for biochemical and molecular studies (Ravid
et al. 1992; Harrison 1996).
Cell Tissue Banking (2007) 8:151–162
155
Clinical and functional assessment
Step 1
Although the 40 min interview is usually done
during the waiting period at SPAS, it may be
rescheduled for a later date during the following
few days, in case of any impediment. The subject’s clinical and functional statuses are assessed
through the CS. The protocol includes a series of
semi-structured scales and questionnaires that
cover major functional abilities and are validated
for assessment with an informant (Table 1)
(Morris et al. 1991; Isella et al. 2006). Additional
information is collected from medical records
when available. Moreover, information concerning demographics, medication, medical history,
cardiovascular risk factors, and family history of
dementia is also collected.
Body weight, height and skull size are measured.
CSF is extracted in situ, from the lateral ventricles
by transcallosal puncture. Blood is taken from the
aorta. Brain, heart, cervical carotids and a kidney
sample are removed.
Neuropathological procedures (Fig. 3)
Step 3
The procedures are divided into three steps: (1)
during autopsy procedure, (2) immediately after
autopsy, and (3) during post-fixation (Fig. 3).
Steps 1 and 2 are done by three alternating
teams composed of three biomedicine undergraduates and one graduate student each. During Step 3, tissue processing and staining are
performed by histotechnicians. The materials
are analyzed macroscopically and microscopically by the pathologists (Fig. 3). Autopsy is
performed by the SPAS pathologist on shift.
All the procedures are done in the BBBABSG’s
laboratory, located one floor above the SPAS.
Any surplus tissue is discarded and buried
according to Brazilian regulations.
Step 2
The brain and heart are measured (weight and
volume) and digitally photographed. Three samples of 1 · 1 cm each are taken from selected
areas are snap frozen in labeled cryotubes
(Table 2). The Circle of Wills is dissected,
photographed and fixed. Subsequently, the brain
(suspended), heart, and carotids are fixed. All the
material is fixed in 4% buffered paraformaldehyde for 3 weeks.
Macroscopic analyzes
Brain
After cerebellum and brainstem separation by a
cut at the level of the superior colliculus, the brain
Table 1 Scales used in Brain Bank of the Brazilian Aging Brain Study Group for the clinical and functional assessment
2006
Domain
Scales
Cognitive
Clinical Dementia Rating Scale—CDR (Morris 1993)
Informant questionnaire of the cognitive decline in the
elderly—IQCODE (Jorm 1994)
Neuropsychiatric Inventory—NPI (Cummings et al. 1994)
DSM IV—SCID for depression and manic disorders
(Del-Ben et al. 1996; Spitzer et al. 1992)
The Katz Index (Katz et al. 1963)
Instrumental activities of daily living (Lawton and Brody 1969)
Tanner et al. (1990)
ABIPEME—a Brazilian scale used to determine social-economic
condition (Almeida and Wickerhauser 1991)
Behavioral changes
Affective disorders
Functional assessment
Parkinson disease
Social information
123
123
Other
tissue
X
X
X
X
X
X
X
X
X
b
Note: Paraffin blocks measure 2.5 · 2.0 · 0.4 cm each
X = sampled; b = bilateral; u = unilateral
X
b
X
b
X
X
X
u
X
X
X
u
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Medulla Cerebellum, Circle Cervical Heart Kidney CSF Arterial
Midbrain Pons
Amygdala Thalamus Basal
Middle Superior Superior Superior Occipital Anterior
carotids
sample
blood
of
including including oblongata including
ganglia,
hippocampal
frontal lobe
and
frontal and
the dentate Willis
locus
including the
(BA17/18) formation,
gyrus
middle
gyrus inferior
nucleus
substantia ceruleus
the
entorhinal
temporal (BA8/9)
(BA46) parietal
nigra
nucleus
region
and
gyrus
lobule
basalis
(BA27/28)
(BA 39/40) (BA21/22) anterior
of
and the
cingulate
Meynert,
inferior
gyrus
at the
temporal
(BA24),
level
gyrus
at the
of the
(BA20)
level
anterior
of the
commissure
anterior
basal
ganglia
Brain
Stored
X
at – 80C b
Stored
at 4C
Fixed
X
Embedded X
in paraffin
Area
Table 2 Types of tissues collected and their respective procedure of sampling—Brain Bank of the Brazilian Aging Brain Study Group. Sao Paulo, 2006
156
Cell Tissue Banking (2007) 8:151–162
Cell Tissue Banking (2007) 8:151–162
157
is coronally sliced in 1 cm slabs. A minimal set of
13 areas is represented and embedded in paraffin
blocks (Table 2). The remaining tissue is stored in
covered plastic boxes.
HE and Masson’s trichromic for assessing signs
of kidney damage due pressure and atherosclerosis.
Histological assessment and diagnosis criteria
Cardiovascular
In order to assess cardiovascular changes which
might be related to cognitive impairment, carotids, coronaries and Circle of Willis’ arteries are
examined semiquantitatively, both macroscopically and microscopically. In every artery, the
atherosclerosis level is graded as: none, mild,
moderate or severe, and the most obstructed part
is sampled and measured microscopically.
The ventricular thickness is measured and the
heart valves are examined for assessing the
occurrence of high blood pressure effects over the
heart. These procedures are performed by a specialist following a protocol.
The histological assessments are based on the
most accepted criteria for age-related neurodegenerative diseases (Mirra et al. 1991; Braak and
Braak 1991; Braak et al. 2004; McKeith et al.
1996; NIA-RR 1997; McKhann et al. 2001; Saito
et al. 2004). Vascular pathology is recorded by
area, size and type.
DNA bank
DNA is extracted from blood samples up to
7 days after the autopsy and is frozen at – 80C.
The DNA procedure is coordinated by Mayana
Zatz, Ph.D., Director of the Human Genomics
Research Center.
Histological technique and staining methods
Eletronic database
All paraffin blocks are sectioned 8 lm thick and
stained with hematoxylin-eosin (HE) and modified Bielschowsky silver impregnation methods.
Routine immunohistochemistry is performed on
selected areas (Table 3) using antibodies against
the following peptides or proteins: b-amyloid,
phosphorylated tau, a-synuclein and ubiquitin
(Table 4). If suspected lesions are found in the
other samples, additional immunostaining is
performed. The kidney sample is stained with
An SQL-based database was built to store and
analyze the data. This work is coordinated by
Helena Brentani, MD, Ph.D., Director of the
Bioinformatics Laboratory of Hospital A.C
Camargo—Sao Paulo. This laboratory has contributed to the building of the Sao Paulo Cancer
Genomics Project’s database (Brentani et al.
2003). Data are loaded in each procedure step.
The database is password protected, and backups
are done daily.
Table 3 Antibodies used routinely in Brain Bank of the Brazilian Aging Brain Study Group
Protein
name
Clone
(source)
Dilution
Antigenal-retrieval
treatment
Detecton
system
Chromogen
b-Amyloid
4G8 (Signet
Pathology
Systems)
1:10,000
Steam,
citrate
pH 6
DAB
Tau
PHF-1
(Gift of
P. Davies)
a-Synuclein
(Chemicon)
1:2,000
Steam, citrate pH 6
1:500
Steam, citrate pH 6
Anti-ubiquitin
polyclonal
(DAKO)
1:5,000
Steam, citrate pH 6
Vectastain
ABC Kit
(Mouse IgG)—Vector
Laboratories
Vectastain
ABC Kit
(Mouse IgG)
Vectastain
ABC Kit
(Mouse IgG)
Vectastain
ABC Kit
(Mouse IgG)
a-Synuclein
Ubiquitin
DAB
DAB
DAB
123
Tissue request
X
X
X
X
X
X
X
X = stained. Ubiquitin immunohistochemistry is performed if Frontotemporal Lobar Degeneration is suspected
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
4G8
X
Tau 2
X
a-Synuclein
Superior
and middle
temporal
gyrus
(BA21/22)
Middle
frontal
gyrus
(BA46)
123
Research groups may access material for studies
on the aging process and related neurodegenerative diseases. The request, together with the proof
of ethics approval from the parent institution, is
evaluated by the BBBABSG core board. An annual report from each participating research
group should be done. No tissue may be redistributed without authorization from the
BBBABSG.
Results
Superior
and
inferior
parietal
lobule
(BA 39/40)
Superior Occipital
frontal
lobe
gyrus
(BA17/18)
(BA8/9)
and
anterior
cingulate
gyrus
(BA24)
Anterior
Amygdala Thalamus Basal
Midbrain Pons
Medulla Cerebellum
hippocampal
ganglia,
including oblongata
formation,
including
locus
entorhinal
the
ceruleus
region
nucleus
(BA27/28)
basalis
and the
of Meynert,
inferior
temporal
gyrus
(BA20)
Cell Tissue Banking (2007) 8:151–162
Area
Table 4 Staining protocol for brain areas. Brain Bank of the Brazilian Aging Brain Study Group 2006
158
Sample characteristics
From April 2004 to December 2005, 1,602 out of
the 2,769 possible subjects were enrolled. The
number of deaths in older age groups as well as
enrolled subjects increased during the winter.
Although the percentage of possible subjects
successfully banked is around 50%, approximately 9% of the NOKs declined to participate in
this study, mainly due a lack of interest in the
proposed study. Possible subjects are excluded by
either CS or subject-dependent variables, such as
lack of reliability or agonal state severity,
respectively. (Fig. 4)
The series mean age is 71.2 years for females
and 66.5 years for males, following the life
expectancy data for Sao Paulo City. However,
males are slightly more represented in general
(Fig. 5).
Table 5 summarizes additional results regarding ethnic distribution.
It is noteworthy that 2/3 of the subjects are
non-cognitive impaired (CDR = 0) (Fig. 6).
The cost per successfully banked specimen was
about US$400 per case.
Tissue request
To date, BBBAGSG is providing tissue for five
kinds of studies: neuropathological, neurochemical, molecular, neuroimaging and epidemiological,
which are being conducted in 14 research laboratories from both USPMS and outside.
Cell Tissue Banking (2007) 8:151–162
Fig. 4 Time line of Brain
Bank of the Brazilian
Aging Brain Study Group
series from April 2004 to
December 2005 (in
absolute numbers)
159
3000
2750
Possible subjects = 2,769
2500
2250
2000
1750
Enrolled subjects = 1,602
1500
1250
Excluded due to selection
criteria = 774
1000
750
500
Excluded due to CS = 295
250
Refused =148
0
jul/04ago/04 set/04 out/04nov/04dez/04 jan/05 fev/05mar/05abr/05mai/05jun/05 jul/05ago/05 set/05 out/05nov/05dez/05 jan/06
Discussion
Our first results show the feasibility of brain bank
based on a large general autopsy service that
prospectively prepares and stores specimens to
satisfy most research requirements for aging
processes and related neurodegenerative studies.
Furthermore, the large amount of available subjects affords strict selection criteria minimizing
the pitfalls related to this kind of study design. In
summary, some local characteristics are positive
assets to BBBABSG, such as:
(a)
The large number of autopsies done at SPAS,
leading to a large number of possible subjects,
consequently facilitating control-case matching and continuous specimen replacement,
(b) The location of SPAS within the USPMS,
adjacent to the Pathology Department,
narrowing postmortem delay and avoiding
transportation damage,
(c) The broad heterogeneity of the Sao Paulo
population, resulting in an ethnically diverse
sample (BBBABSG hosts 160 African and
19 Oriental subjects.),
Fig. 5 Brain Bank of the
Brazilian Aging Brain
Study Group series.
Subjects’ distribution by
gender and age group
123
160
Cell Tissue Banking (2007) 8:151–162
Table 5 Ethnic group distribution—Brain Bank of the
Brazilian Aging Brain Study Group 2004–2006
65.7%
Ethnic group
(%)
African
Caucasian
Mixed
Orientals
Not available
10
76.6
11
1.2
1.2
The large amount of control subjects
(65.7%), a group extremely important to
neurodegenerative disease studies and scarcely represented in some series (Murphy
and Ravina 2003; Ravid et al. 1995). Furthermore, most of the mild affected subjects
are drug-naı̈ve,
(e) The high quality of material obtained with
low maintenance costs. Each successfully
banked specimen cost US$400 in direct and
indirect cost, while in the USA the costs range
from $10,000 to $30,000 (Hulette 2003). Given that SPAS is an already-established service which boasts structured technical support,
the costs are due to consumables, and
(f) Complete autopsy results and objective cardiovascular evaluation—even careful clinical
and laboratory assessment may show discrepancies with autopsy data (Roulson et al.
2005). Given that some cardiovascular risk
factors are implied in dementia (Luchsinger
et al. 2005), a number of studies stress the
importance of objective vascular evaluation
through autopsy.
12.6%
(d)
8.2%
CDR0
CDR 0.5
CDR 1
5.4%
CDR 2
8.1%
CDR 3
Fig. 6 Subject distribution according to the Clinical
Rating Scale of Dementia. Brain Bank of the Brazilian
Aging Brain Study Group 2004–2006
Cognitive function is a difficult assessment area,
especially in the absence of the subject. Therefore, aiming to gather reliable data from the CS,
our protocol comprises only scales which are
widely recognized as reliable for informantbased assessment (Morris et al. 1991; Jorm 1997;
Winblad et al. 2004), including two cognitive
scales: the IQCODE (Jorm 1994) and the CDR
(Morris 1993). A study performed in Sao Paulo
City verifies the IQCODE high sensitivity and
specificity to the local population (Bustamante
et al. 2003). Furthermore, evidence demonstrates
these scales to be reliable even for subjects
having mild cognitive impairment (Isella et al.
2006).
An assessment done by experienced gerontologists is considered as accurate as one done by
physicians (McCulla et al. 1989).
The desirable design for a neurodegenerative
brain bank is based on longitudinally assessed
subjects. However, most brain banks are affected
by low rates of subject enrollment. These low
rates result in a lack of matching control cases,
and long periods are needed to gather a reasonable amount of samples. Therefore, a cross-sectional design could solve some of the cited
problems and even complement the other series
through collaborations.
We try to tackle the following questions/issues:
(2)
(1)
USPMS is a government-supported school. The
BBBABSG is sponsored by grants from
the Pathology Department and minor grants from
Is a cross-sectional brain bank in which clinical and functional assessment is based on CS
information able to provide reliable data?
123
Is the period during autopsy suitable for
clinical and functional assessment?
Both the previous pilot studies and the current
experience demonstrate that CSs are cooperative
and provide accurate information in this period.
Around 90% of the families voluntarily consent
to participate, and just 15% of the assessments
are reassigned for a few days later.
(3)
Is a structured brain bank affordable in local
research conditions?
Cell Tissue Banking (2007) 8:151–162
the Brazilian Research Institutes; SPAS structure
and staff is paid by public funds.
Moreover, the majority of the collecting and storing procedures are performed by supervised
undergraduate biomedical students enrolled in a
certificated Research Training Program. These
students spend 20 h per week in training, and 30%
of that time is dedicated to BBBABSG. The students receive a scholarship, and the remaining time
is dedicated to their research projects, seminars
and lectures. Those students are more academically prepared and motivated than technicians.
Furthermore, several requests for grants are under
evaluation by both national and international
associations, as well as private companies which
might benefit from tax breaks.
Conclusions
The high percentage of control subjects and the
ethnic diversity of this series might make a significant contribution toward understanding aging
brain processes and related neurodegenerative
diseases. BBBABSG is not another brain bank in
competition with the established facilities; rather,
BBBABSG outcomes may provide investigators
the answers to some additional questions. Finally,
the BBBABSG series has the potential to advance the knowledge and understanding of the
mechanisms underlying aging brain processes and
related neurodegenerative diseases.
Acknowledgements We are grateful to Prof. H. Heinsen (Julius Maximilians University Wurzburg, Germany)
and to Larenda Mielke (Washington University in St
Louis, USA) for them critical review. We also thank Sao
Paulo Autopsy Service physicians and staff for unconditional support, BBASG’s students for outstanding
assistance and the staff of Pathology Department of
University of Sao Paulo Medical School for technical
support.Support for this work was provided by grants
from the Pathology Department and Geriatrics Division
of University of Sao Paulo Medical School Research and
Teaching Institute of Albert Einstein Hospital (Sao
Paulo), Toxicology Department of Butantan Institute
(Sao Paulo), Coordenadoria de Apoio ao Pessoal de
Nivel Superior—CAPES Scholarship (to LTG), and
Fundação de Apoio à Pesquisa do Estado de São Paulo
– FAPESP Scholarship (to LTG).
161
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