The Association of Cognitive Endophenotypes and Risky Single Nucleotide Polymorphisms of Alzheimer's Disease within the Alzheimer's Disease Neuroimaging Initiative (ADNI) Database
Year: 2015
Type: article
Abstract: Objective: The purpose of this study was to assess the influence of three single nucleotide polymorphisms (SNP) previously associated with Alzheimer's disease on specific domains of cognition, when controlling for Apolipoprotein E gene (APOE), in a sample of individuals with Alzheimer's disease. Methods: The data were drawn from the Alzheimer's Disease Neuroimaging Initiative database, a comprehensive, longitudinal database of controls, persons with mild cognitive impairment, and persons with mild Alzheimer's disease. Each subject has a full neuropsychological assessment, neuroimaging, genetic sequencing, and physical evaluation. For the purposes of this study, individuals were selected based on the presence of the three SNPs of interest: CR1 (rs3818361_T), CLU (rs11136000_T), and PICALM (rs3851179_A). Each SNP was then measured against the available tests of the ADNI neuropsychological battery that measured immediate and long delay memory, semantic fluency, and confrontation naming. Results: Only the CR1 SNP (rs3818361_T) had significant findings. The presence of the CR1 SNP associated with lower performance on logical memory recall total score, AVLT immediate recall trials 2 and 4, AVLT delayed recall, and confrontation naming in the 12-month control group. Logical memory and AVLT delayed recall were also negatively associated with CR1 in the 12-month AD case group. Discussion: These results support previous findings that the CR1 SNP rs3818361_T is a risk factor for cognitive impairment in individuals with and without AD. Such findings can aid in the earlier detection of Alzheimer's disease, risk for domain specific cognitive impairment, and novel targets for personalized pharmacotherapy.
Author: Kyle J. Jennette
Institution: University of South Florida
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Defense, Alzheimer's Association, Bristol-Myers Squibb, Eli Lilly and Company, Biogen, University of Southern California, F. Hoffmann-La Roche, Alzheimer's Disease Neuroimaging Initiative, BioClinica, Northern California Institute for Research and Education, Eisai, National Institutes of Health, University of California, San Diego
Awards: G1012222616, G1554142629, G1650819308, G2152643862, G2189010064, G2340207221, G2423387114, G2835601961, G29951154, G3131374986, G3216574877, G3553156159, G3710456697, G3966393351, G4119534169, G43180419, G4475667458, G4800177743, G5207404921, G5365730499, EFFECTS OF TRAUMATIC BRAIN INJURY (TBI) AND POST TRAUMATIC STRESS DISORDER (PTSD) ON ALZHEIMER'S DISEASE (AD) IN VETERANS USING IMAGING AND BIOMARKERS IN THE AD NEUROIMAGING INITIATIVE (ADNI)", G5654639750, G5850682332, G6210868510, G6371410416, G6792506723, G6899163935, G6948409098, G72415811, G764699806, G781725486, G8228018387, G8895907669, G8897063270, G8957659042, G9000039018, G9000122335
OpenAlex ID: W768481572