Project: Research project

Project Details


Alzheimer disease is the leading cause of dementia in the elderly,
affecting more than 4 million individuals in the U.S. alone. A genetic
component has long been indicated in the etiology of the disease and has
been supported in a number of genetic and epidemiological studies.
Although some families show clear evidence of autosomal dominant
inheritance, many others are equivocal, and thus the mode of inheritance
of familial Alzheimer disease (FAD) is not well established. One gene
for FAD has been identified (APP), but it accounts for less than 2% of
FAD cases, and no other genes have yet been identified, although a
location on chromosome 19 has been proposed. Through the efforts of the
Human Genome Initiative, it is now possible to efficiently screen the
entire genome for genes associated with FAD. The goal of the present proposal is to perform an efficient screen of the
entire genome in order to identify all the major loci involved in FAD.
Both early and late onset families will be incorporated into the
screening process. A multicenter approach will be used to rapidly
generate the necessary marker data, and to rapidly and efficiently
perform the statistical analyses on these data. Since the emphasis of
this proposal is on the analysis of the resulting data, only well-defined
marker systems will be used and no effort will be expended to generate
new markers. This approach will allow us to fully exploit the efforts
of the Human Genome Initiative, thereby helping to fulfill its promise. A hierarchical structure for genotyping of the families will be
established. Initially, a core set of families will be identified that
have sufficient power to generate significant standard linkage results.
Additional pedigrees with only a few affected individuals will be used
for a variety of state of the art statistical methodologies including
affected-pedigree-member (APM) analysis, sib-pair linkage studies as well
as maximum likelihood methods inclusive of two locus models. Examination
for and effects of heterogeneity and age of onset will also be
incorporated into the study. The ultimate goal of the proposed research
is the identification of all major loci involved in FAD etiology, as the
first step in combatting this devastating disorder of the elderly.
Effective start/end date1/1/931/31/10


  • National Institutes of Health: $524,265.00
  • National Institutes of Health: $515,817.00
  • National Institutes of Health: $529,367.00
  • National Institutes of Health: $520,878.00
  • National Institutes of Health: $526,492.00


  • Medicine(all)
  • Neuroscience(all)


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