title: Potential contribution of the Alzheimer's disease risk locus BIN1 to episodic memory performance in cognitively normal Type 2 diabetes elderly.
abstract: In recent years, several promising susceptibility loci for late-onset Alzheimer's disease (AD) were discovered, by implementing genome-wide association studies (GWAS) approach. Recent GWAS meta-analysis has demonstrated the association of 19 loci (in addition to the APOE locus) with AD in the European ancestry population at genome-wide significance level. Since Type 2 Diabetes (T2D) is a substantial risk factor for cognitive decline and dementia, the 19 single nucleotide polymorphisms (SNPs) that represent the 19 AD loci were studied for association with performance in episodic memory, a primary cognitive domain affected by AD, in a sample of 848 cognitively normal elderly Israeli Jewish T2D patients. We found a suggestive association of SNP rs6733839, located near the bridging integrator 1 (BIN1) gene, with this phenotype. Controlling for demographic (age, sex, education, disease duration and ancestry) covariates, carriers of two copies of the AD risk allele T (TT genotype) performed significantly worse (p=0.00576; p=0.00127 among Ashkenazi origin sub-sample) in episodic memory compared to carriers of the C allele (CT+CC genotypes). When including additional potential covariates (clinical and APOE genotype), results remained significant (p=0.00769; p=0.00148 among Ashkenazi). Interestingly, as validated in multiple large studies, BIN1 is one of the most established AD risk loci, with a high odds ratio. Although preliminary and require further replications, our findings support a contribution of BIN1 to individual differences in episodic memory performance among T2D patients.
authors.affiliation: Department of Neurology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. Electronic address: liorgreenbaum@yahoo.com.
authors.forename: Lior
authors.initials: L
authors.lastname: Greenbaum
authors.affiliation: The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; Memory Clinic, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ramit
authors.initials: R
authors.lastname: Ravona-Springer
authors.affiliation: The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
authors.forename: Irit
authors.initials: I
authors.lastname: Lubitz
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: James
authors.initials: J
authors.lastname: Schmeidler
authors.affiliation: The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
authors.forename: Itzik
authors.initials: I
authors.lastname: Cooper
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Sano
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Silverman
authors.affiliation: Department of Family Medicine, Tel Aviv University, Tel Aviv, Israel; Maccabi Health Services, Israel.
authors.forename: Anthony
authors.initials: A
authors.lastname: Heymann
authors.affiliation: The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Michal Schnaider
authors.initials: MS
authors.lastname: Beeri
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D003071:Cognition / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000523:psychology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D061212:Memory, Episodic; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012306:Risk; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C101410:BIN1 protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins
keywords: Alzheimer׳s disease; BIN1; Episodic memory; Type 2 diabetes