Abstract Details

Title Association Study of Late-Onset Alzheimer's Disease Risk Variants and Memory Decline

Topic Aging and Dementia

Presentation(s) (-)

Poster/Presentation
Number 006

Objective

Background Recent GWAS of LOAD case-control series identified single nucleotide polymorphisms (SNPs) at nine loci which associate with disease risk. Investigation of these variants for their influence on AD-related endophenotypes may provide valuable information regarding downstream biological consequence of such genetic variation.

Design/Methods We assessed a prospectively collected series of 1,441 Caucasian subjects from the Mayo Clinic Study of Aging (MCSA) by genotyping the top 9 LOAD risk SNPs from the nine LOAD GWAS loci and investigating associations with slopes of change in logical memory delayed recall scores from the Wechsler Memory Scale-Revised, collected longitudinally. Mixed effects models were used to estimate individual slopes (random) and intercepts (fixed). These were used in linear regression to assess associations of genotypes with cognitive slopes, adjusting for age, sex, APOE4 dosage, years of education, and diagnosis.

Results APOE ?4 dose was a significant covariate in all models with negative memory slope estimates, as expected (p<1.4E-3). CD33 rs3865444 (p=0.019) and BIN1 rs744373 (p=0.028) SNPs had nominally significant associations with negative memory slope estimates. BIN1 risky allele was associated with more negative slopes, although it was CD33 protective allele that had more negative memory slope estimates, indicating faster memory declines.

Conclusions Our results suggest that the use of memory slopes from longitudinally collected series might be a valuable endophenotype in assessing the role of LOAD risk variants in human cognition. These results need to be confirmed in similar series. Further, additional cognitive slopes and combined genotype scores need to be evaluated in these and other series.

Authors/Disclosures
Minerva Carrasquillo (Mayo Clinic Florida) PRESENTER	Minerva Carrasquillo has nothing to disclose.
Richard S. Finkel, MD, FAAN (St. Jude Children's Research Hospital)	Dr. Finkel has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AveXis. Dr. Finkel has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Catabasis. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Capricor. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ReveraGen. Dr. Finkel has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Scholar Rock. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Finkel has received research support from AveXis. The institution of Dr. Finkel has received research support from Biogen. The institution of Dr. Finkel has received research support from Capricor. The institution of Dr. Finkel has received research support from Catabasis. The institution of Dr. Finkel has received research support from ReveraGen. The institution of Dr. Finkel has received research support from Roche. The institution of Dr. Finkel has received research support from Scholar Rock. Dr. Finkel has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Finkel has received intellectual property interests from a discovery or technology relating to health care. Dr. Finkel has received personal compensation in the range of $0-$499 for serving as a Speaker in workshop with National Academy of Sciences. Dr. Finkel has a non-compensated relationship as a advisor with n-Lorem Foundation that is relevant to AAN interests or activities. Dr. Finkel has a non-compensated relationship as a Board Member with EveryLife Foundation that is relevant to AAN interests or activities.
	No disclosure on file
Otto Pedraza (Mayo Clinic)	The institution of Otto Pedraza has received research support from Alzheimer's Association. Otto Pedraza has received publishing royalties from a publication relating to health care.
	No disclosure on file
Mariet Allen, PhD (Mayo Clinic)	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Rosebud O. Roberts, MD (Mayo Clinic)	No disclosure on file
John A. Lucas	John A. Lucas has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for American Board of Clinical Neuropsychology.
Robert J. Ivnik, PhD (Psychology Division (West 11-B))	No disclosure on file
Mary M. Machulda, PhD (Mayo Clinic)	The institution of Dr. Machulda has received research support from NIH.
Neill R. Graff-Radford, MD, FAAN (Mayo Clinic Jacksonville)	The institution of Dr. Graff-Radford has received research support from Biogen. The institution of Dr. Graff-Radford has received research support from Lilly. The institution of Dr. Graff-Radford has received research support from Eisai. The institution of Dr. Graff-Radford has received research support from Biogen. Dr. Graff-Radford has received publishing royalties from a publication relating to health care.
Ronald C. Petersen, MD, PhD, FAAN (Mayo Clinic)	Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly and Co.. Dr. Petersen has received personal compensation in the range of $0-$499 for serving as a Consultant for Eisai, Inc.. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novo Nordisk. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Petersen has received publishing royalties from a publication relating to health care. Dr. Petersen has received publishing royalties from a publication relating to health care. Dr. Petersen has received publishing royalties from a publication relating to health care. Dr. Petersen has a non-compensated relationship as a Board of Directors with American Brain Foundation that is relevant to AAN interests or activities.
Steven G. Younkin, MD, PhD (Mayo Clinic Jacksonville)	No disclosure on file
Nilufer Taner, MD, PhD, FAAN (Mayo Clinic)	The institution of Dr. Taner has received research support from NIH.

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