Abstract Details

Title Association of the Tauopathy GWAS Loci with Alzheimer's Disease in China

Topic Aging and Dementia

Presentation(s) P04 - (-)

Poster/Presentation
Number 220

Objective

Background BACKGROUND: Both AD and PSP are a class of neurodegenerative diseases with prominent tau neuropathology. A recent PSP GWAS identified several common genetic variations within the STX6, MOBP, MAPT and EIF2AK3 genes contributing to risk for tauopathies. The expression levels and functional features of these genes exclusively supported their associations with PSP.

Design/Methods DESIGN/METHODS: We recruited 1,592 unrelated Northern Han Chinese individuals comprising 796 patients with a clinical diagnosis of LOAD and 796 healthy age- and sex-matched controls. The selected SNPs in STX6, MOBP, EIF2AK3 and MAPT were genotyped with the method of polymerase chain reaction-ligase detection reaction (LDR) on an ABI Prism 377 Sequence Detection System.

Results RESULTS: Rs242557 at the MAPT locus was associated with late-onset AD (LOAD) (OR = 1.175, P = 0.026), which appeared to be stronger for LOAD patients with apolipoprotein E (APOE) ?4 allele (OR = 1.510). And this positive association was not changed after adjusting for age, gender and the APOE ?4-carrier status (additive model: OR = 1.163, P = 0.036; dominant model: OR = 1.315, P = 0.010). Rs1768208 in MOBP and rs7571971 in EIF2AK3 showed association only in the APOE ?4 positive subjects, and these did not appear to be independent of APOE. As for rs1411478 in STX6, we did not explore any association with LOAD.

Conclusions CONCLUSIONS: Our exploratory analysis mainly suggests an association of MAPT with LOAD, especially in APOE ?4 carriers. Genotypes at MOBP and EIF2AK3 confer risk predominantly in APOE ?4-positive subjects, with indications of an interaction between APOE and MOBP or EIF2AK3 on AD risk.

Authors/Disclosures
PRESENTER	No disclosure on file
Jin-Tai Yu	No disclosure on file
Lan Tan (Affiliated Hospital of Qingdao Medical College)	No disclosure on file
Mark Hallett, MD, FAAN (National Institutes of Health)	Dr. Hallett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Hallett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurocrine. Dr. Hallett has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Brainsway. Dr. Hallett has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for VoxNeuro. Dr. Hallett has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for QuantalX. Dr. Hallett has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Hallett has received intellectual property interests from a discovery or technology relating to health care. Dr. Hallett has received publishing royalties from a publication relating to health care. Dr. Hallett has received publishing royalties from a publication relating to health care. Dr. Hallett has received publishing royalties from a publication relating to health care. Dr. Hallett has received publishing royalties from a publication relating to health care. Dr. Hallett has received personal compensation in the range of $500-$4,999 for serving as a Speaker with International Parkinson and Movement Disorder Society. Dr. Hallett has a non-compensated relationship as a Past-President with Functional Neurological Disorder Society that is relevant to AAN interests or activities.

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