The identification of mutations in the APP, PS1, and PS2 genes that cause early-onset familial Alzheimer's disease (AD), the demonstration that these mutations all increase Abeta42, and the discovery of an association between Apolipoprotein E4 and late-onset Alzheimer's disease have dramatically improved our understanding of Alzheimer's disease. It is clear, however, that much of the genetic risk in late onset Alzheimer's disease remains unexplained. Current strategies to identify other genes that affect late-onset Alzheimer's disease have met with limited success often because of the difficulty associated with obtaining late-onset families with sufficient power for reliable linkage analysis. Genetic studies using large numbers of small families or sib-pairs, to increase the power of the analysis, are also currently being performed by several groups however difficulties with the non-replication of positive loci, identified by different studies, has continued. It will also be difficult to identify the biologically relevant genetic variability using loci identified by this type of small family/sib pair analysis, as candidate regions tend to be large and poorly defined. In this proposal we describe how high plasma ABeta levels can be used as a surrogate phenotype to increase the power of late-onset AD families allowing not only the reliable linkage of a specific chromosomal region with disease but also facilitating the identification of the genetic variability that is responsible for the increased plasma Abeta42 and for the increased risk of developing Alzheimer's disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG018023-01A1
Application #
6266739
Study Section
Special Emphasis Panel (ZRG1-BDCN-3 (01))
Program Officer
Miller, Marilyn
Project Start
2001-03-15
Project End
2006-02-28
Budget Start
2001-03-15
Budget End
2002-02-28
Support Year
1
Fiscal Year
2001
Total Cost
$348,075
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
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