Hippocampal Sclerosis of Aging, a Common Alzheimer's Disease 'Mimic': Risk Genotypes are Associated with Brain Atrophy Outside the Temporal Lobe
dc.contributor.author | Nho, Kwangsik | |
dc.contributor.author | Saykin, Andrew J. | |
dc.contributor.author | Nelson, Peter T. | |
dc.contributor.department | Department of Radiology and Imaging Sciences, IU School of Medicine | en_US |
dc.date.accessioned | 2017-06-08T14:47:55Z | |
dc.date.available | 2017-06-08T14:47:55Z | |
dc.date.issued | 2016 | |
dc.description.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. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Nho, K., Saykin, A. J., Alzheimer’s Disease Neuroimaging Initiative, & Nelson, P. T. (2016). Hippocampal Sclerosis of Aging, a Common Alzheimer’s Disease “Mimic”: Risk Genotypes are Associated with Brain Atrophy Outside the Temporal Lobe. Journal of Alzheimer’s Disease : JAD, 52(1), 373–383. http://doi.org/10.3233/JAD-160077 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/12916 | |
dc.language.iso | en_US | en_US |
dc.publisher | IOS Press | en_US |
dc.relation.isversionof | 10.3233/JAD-160077 | en_US |
dc.relation.journal | Journal of Alzheimer’s Disease | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | Arteriolosclerosis | en_US |
dc.subject | Dementia | en_US |
dc.subject | KATP | en_US |
dc.subject | Progranulin | en_US |
dc.subject | rs5848 | en_US |
dc.subject | rs704180 | en_US |
dc.subject | rs1990622 | en_US |
dc.subject | rs9637454 | en_US |
dc.subject | SUR2 | en_US |
dc.subject | TDP-43 | en_US |
dc.title | Hippocampal Sclerosis of Aging, a Common Alzheimer's Disease 'Mimic': Risk Genotypes are Associated with Brain Atrophy Outside the Temporal Lobe | en_US |
dc.type | Article | en_US |