AVAILABILITY OF THE NIMH ALZHEIMER'S DISEASE GENETICS DATASET

NIH GUIDE, Volume 24, Number 23, June 23, 1995



P.T. 34



Keywords:

  Genetics 

  Senile Dementia 

  Registries+ 



National Institute of Mental Health



The National Institute of Mental Health (NIMH), recognizing the major

public health implications of identifying genes responsible for

severe neuropsychiatric disorders, has funded a multi-site Genetics

Initiative.  The goal of this Initiative is to establish a national

resource of demographic, clinical, and genetic data from individuals

with Alzheimer's disease (AD), schizophrenia, or bipolar disorder to

aid researchers in defining the genetic bases for these disorders.



This notice announces the availability on July 1, 1995 of clinical

data and DNA from the NIMH AD Genetics Dataset to qualified

investigators studying the genetics of Alzheimer's disease.  As of

May 31, 1995, the NIMH AD Genetics Dataset contained clinical data

and DNA on 238 sib-pairs.  The Alzheimer's disease genetics catalog

will be available via Internet (http://nimh.sratech.com).  Genotyping

results will become available at a later date.



Alzheimer's disease sib-pairs are identified via cooperative

agreements to the University of Alabama at Birmingham, Johns Hopkins

University, and Massachusetts General Hospital.  Data being collected

consist of clinical information, including demographics,

symptomatology, and eventually autopsy data, which are being stored

in a central Data Management Center, and genetic materials stored at

the NIMH Cell Repository.  These latter resources have been

established through contract mechanisms.



Data collection from AD sib-pairs and unaffected siblings has been

coordinated among the three university-based Diagnostic Centers using

an agreed-upon protocol that has included uniform assessments,

extensive interview data on risk factors and medical history, and

shared rules for extension of pedigrees through affected members.

There have been two methods of ascertainment employed by each site.

The first method is systematic, e.g., all patients evaluated within a

clinical population are screened for the possible availability of a

secondary proband within the family.  The second method is

opportunistic.  This method uses several mechanisms to identify

families:  referral from other clinicians, contacting local AD

associations, and media advertising.  There is a preferential

ascertainment scheme based on family structure, which is dictated by

the methods of linkage analysis.  The order of preference is (1)

those families with living affected sib-pairs; (2) those families

with one living affected sib and one deceased sib with recoverable

tissue for DNA genotyping and with another living affected relative

no more distantly related than biological first-cousins; (3) those

families with a proband and an affected relative no more distantly

related than biological first-cousins with living affected relatives

in the line of descent; (4) same as 3 but with deceased affected

relatives in the line of descent.



These Centers have the ability to follow subjects longitudinally,

track changes in diagnoses, and compare and update diagnoses by

autopsy, thus avoiding false positives, a major pitfall to genetic

studies.  To be eligible for inclusion in the study, primary probands

must meet NINCDS-ADRDA criteria for probable Alzheimer's disease on

initial evaluation and show deterioration in cognitive function by

longitudinal assessment or history for at least one year.  The

secondary proband must meet NINCDS-ADRDA criteria for probable or

possible AD at the onset of disease and have evidence of progressive

decline in cognitive function.  One of the above must have a

Mini-Mental State Examination score less than 27 and history of

difficulties with activities of daily living.  Families with evidence

of bilineal inheritance will be noted.  Probands with depression will

be kept as subjects.



Access to National Resource Data and DNA



Clinical information and DNA will be distributed only to experienced,

qualified investigators who are conducting research on the genetics

of Alzheimer's disease and are associated with a recognized

biomedical research facility.  This NIMH Genetics Initiative clinical

information and DNA obtained by the investigator cannot be

transferred in any manner, with or without charge, to anyone outside

the direct supervision of the principal investigator, without the

express written permission from the NIMH Cell Repository project

officer.



Investigators may request grant funding and access to the clinical

data and DNA by submitting a research grant application to NIMH for

peer review using investigator initiated grant application

mechanisms.  If funding is not requested, contact Dr. Mary Farmer for

information on how to obtain the AD clinical data and DNA.  The cost

of DNA for investigators not funded by an NIMH grant is $50 per 50

microgram vial.  (DNA is shipped only in 50 microgram vials.)



INQUIRIES



For further information, contact:



Mary Farmer, M.D., M.P.H.

Division of Epidemiology and Services Research

National Institute of Mental Health

Parklawn Building, Room 10C-09

5600 Fishers Lane

Rockville, MD  20857

Telephone:  (301) 443-3774

FAX:  (301) 443-4045

Email:  [email protected]



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