Journal of Alzheimer's Disease - Volume 52, issue 1

Authors: Nho, Kwangsik | Saykin, Andrew J. | Alzheimer’s Disease Neuroimaging Initiative | Nelson, Peter T.

Article Type: Research Article

Abstract: Hippocampal sclerosis of aging (HS-Aging) is a common brain disease in older adults with a clinical course that is similar to Alzheimer’s disease. Four single-nucleotide polymorphisms (SNPs) have previously shown association with HS-Aging. The present study investigated structural brain changes associated with these SNPs using surface-based analysis. Participants from the Alzheimer’s Disease Neuroimaging Initiative cohort (ADNI; n  = 1,239), with both MRI scans and genotype data, were used to assess the association between brain atrophy and previously identified HS-Aging risk SNPs in the following genes: GRN , TMEM106B , ABCC9 , and KCNMB2 (minor allele frequency for each is >30%). …A fifth SNP (near the ABCC9 gene) was evaluated in post-hoc analysis. The GRN risk SNP (rs5848_T) was associated with a pattern of atrophy in the dorsomedial frontal lobes bilaterally, remarkable since GRN is a risk factor for frontotemporal dementia. The ABCC9 risk SNP (rs704180_A) was associated with multifocal atrophy whereas a SNP (rs7488080_A) nearby (∼50 kb upstream) ABCC9 was associated with atrophy in the right entorhinal cortex. Neither TMEM106B (rs1990622_T), KCNMB2 (rs9637454_A), nor any of the non-risk alleles were associated with brain atrophy. When all four previously identified HS-Aging risk SNPs were summed into a polygenic risk score, there was a pattern of associated multifocal brain atrophy in a predominately frontal pattern. We conclude that common SNPs previously linked to HS-Aging pathology were associated with a distinct pattern of anterior cortical atrophy. Genetic variation associated with HS-Aging pathology may represent a non-Alzheimer’s disease contribution to atrophy outside of the hippocampus in older adults. Show more

Keywords: Arteriolosclerosis, dementia, KATP, progranulin, rs5848, rs704180, rs1990622, rs9637454, SUR2, TDP-43

DOI: 10.3233/JAD-160077

Citation: Journal of Alzheimer's Disease, vol. 52, no. 1, pp. 373-383, 2016

Article Type: Other

DOI: 10.3233/JAD-160202

Citation: Journal of Alzheimer's Disease, vol. 52, no. 1, pp. 385-389, 2016