Validating predicted biological effects of Alzheimer's disease associated SNPs using CSF biomarker levels.

Journal of Alzheimer's Disease : JAD
John S K KauweAlison M Goate

Abstract

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-β (Aβ) 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) Aβ or tau levels in 602 samples from two independent CSF series. We failed to detect association between CSF Aβ42 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 Aβ42 levels. This association is consistent with previous reports that this non-synonymous coding substitution results in increased Aβ levels in vitro and provides support for an Aβ-related mechanism for modulating risk for Alzheimer's disease.

Citations

Aug 10, 2011·Archives of Neurology·Carlos CruchagaUNKNOWN Alzheimer's Disease Neuroimaging Initiative
Jul 24, 2012·Human Molecular Genetics·Carlos CruchagaAlison M Goate
Apr 8, 2011·Science Translational Medicine·David M HoltzmanAlison M Goate
Oct 15, 2011·Dementia and Geriatric Cognitive Disorders·Panagiotis AlexopoulosRobert Perneczky
Apr 28, 2012·Neurology·S BarralUNKNOWN National Institute on Aging Late-Onset Alzheimer's Disease Genetics Study
Apr 15, 2014·Current Genetic Medicine Reports·Carlos CruchagaJohn S K Kauwe
Mar 12, 2013·TheScientificWorldJournal·Benoît Leclerc, Abedelnasser Abulrob
Oct 5, 2013·Brain Imaging and Behavior·Li ShenUNKNOWN Alzheimer’s Disease Neuroimaging Initiative
Apr 14, 2016·Scientific Reports·Valérie VingtdeuxPhilippe Marambaud

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