Abstract Details

Title Common Variants in ABCA7, MS4A6A, and PICALM Are Associated with Cortical Atrophy

Topic Aging and Dementia

Presentation(s) (-)

Poster/Presentation
Number 001

Objective

Background Alzheimer's disease (AD) is the most common neurodegenerative disease and the leading cause of dementia. Recently genome-wide association studies (GWAS) discovered several new AD risk variants. We studied the relationship between common variants in the top 10 AD risk genes - APOE, BIN1, CLU, ABCA7, CR1, PICALM, MS4A6A, CD33, MS4A4E and CD2AP, and cortical atrophy as a marker of neurodegeneration.

Design/Methods ImaGene is an ongoing longitudinal project aiming to identify the associations between imaging and genetic biomarkers in AD. Structural magnetic resonance imaging and 1-million SNP genotyping on Illumina Human Omni-Quad arrays were performed on 49 cognitively normal (NC) and 87 mild cognitively impaired (MCI) ImaGene subjects. Cortical thickness measurements were obtained at each point on the hemispheric surfaces after explicit matching of cortical morphology. Associations between the top 10 GWAS hits and cortical atrophy were explored using linear regression. Map-wise statistical significance was determined with permutations using threshold of p<0.01.

Results Three of the ten risk-associated variants - PICALM (rs3851179), MS4A6A (rs610932), and ABCA7 (rs376450) - showed significant associations with cortical thickness in the ImaGene sample in the expected direction. MS4A6A allele C showed significant negative associations with cortical thickness of the frontal (BA 6,4,44,45,46), lateral temporal (BA 22,37,41,42), and medial temporo-occipital association cortices (BA 20, 37) (left pcorrected=0.06; right pcorrected=0.033). ABCA7 allele T was associated with left greater then right cortical thinning of BA 9,10 in the frontal lobes (left pcorrected=0.037; right pcorrected=0.09). PICALM allele A showed significant positive association with right anterior temporal (BA 38,20,37,36) and inferior frontal (BA 47, 45) cortical thickness (right pcorrected= 0.02).

Conclusions To our knowledge this is the first report of associations between common variants in PICALM, ABCA7, and MS4A6A and MRI measure of neurodegeneration.

Authors/Disclosures
PRESENTER	No disclosure on file
Kristy Hwang	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Eric Klein	No disclosure on file
	No disclosure on file
Giovanni Coppola, MD (UCLA)	Dr. Coppola has received personal compensation for serving as an employee of Regeneron. Dr. Coppola has received stock or an ownership interest from Regeneron.
Paul M. Thompson, PhD (USC)	No disclosure on file
Liana Apostolova, MD, FAAN (Indiana University School of Medicine)	Dr. Apostolova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NIH. Dr. Apostolova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Apostolova has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Apostolova has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. Dr. Apostolova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Apostolova has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Apostolova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Apostolova 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 Alzheimer Association. An immediate family member of Dr. Apostolova has stock in Cassava Neurosciences. The institution of Dr. Apostolova has received research support from Roche Diagnostics. The institution of Dr. Apostolova has received research support from NIA. The institution of Dr. Apostolova has received research support from Alzheimer Association. The institution of Dr. Apostolova has received research support from AVID radiopharmaceuticals. The institution of Dr. Apostolova has received research support from Life Molecular Imaging.
Roopali Gandhi, PhD (Sanofi Genzyme)	No disclosure on file

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