Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 21, Issue 3, Pages 833-842Publisher
IOS PRESS
DOI: 10.3233/JAD-2010-091711
Keywords
Alzheimer's disease; amyloid; association; CALHM1; endophenotypes; GAB2; genetics; SORL1; tau
Categories
Funding
- National Institutes of Health, Washington University [P50-AG05681, P01-AG03991, P01-AG026276, R01-AG16208, P30-N5057105, 1-TL1-RR024995-01, 1-KL2-RR024994-01]
- NATIONAL CENTER FOR RESEARCH RESOURCES [TL1RR024995, KL2RR024994, UL1RR024992] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [T32MH014677] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [P30NS057105] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [U19AG010483, P50AG005681, R01AG016208, P01AG026276, U01AG024904, U24AG021886, P01AG003991] Funding Source: NIH RePORTER
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Recent large-scale genetic studies of late-onset Alzheimer's disease have identified risk variants in CALHM1, GAB2, and SORL1. The mechanisms by which these genes might modulate risk are not definitively known. CALHM1 and SORL1 may alter amyloid-beta (A beta) levels and GAB2 may influence phosphorylation of the tau protein. In this study we have analyzed disease associated genetic variants in each of these genes for association with cerebrospinal fluid (CSF)A beta or tau levels in 602 samples from two independent CSF series. We failed to detect association between CSF A beta(42) levels and single nucleotide polymorphisms in SORL1 despite substantial statistical power to detect association. While we also failed to detect association between variants in GAB2 and CSF tau levels, power to detect this association was limited. Finally, our data suggest that the minor allele of rs2986017, in CALHM1, is marginally associated with CSF A beta(42) levels. This association is consistent with previous reports that this non-synonymous coding substitution results in increased A beta levels in vitro and provides support for an A beta-related mechanism for modulating risk for Alzheimer's disease.
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