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The effect of increased genetic risk for Alzheimer's disease on hippocampal and amygdala volume.

ABSTRACT: Reduction in hippocampal and amygdala volume measured via structural magnetic resonance imaging is an early marker of Alzheimer's disease (AD). Whether genetic risk factors for AD exert an effect on these subcortical structures independent of clinical status has not been fully investigated. We examine whether increased genetic risk for AD influences hippocampal and amygdala volumes in case-control and population cohorts at different ages, in 1674 older (aged >53 years; 17% AD, 39% mild cognitive impairment [MCI]) and 467 young (16-30 years) adults. An AD polygenic risk score combining common risk variants excluding apolipoprotein E (APOE), and a single nucleotide polymorphism in TREM2, were both associated with reduced hippocampal volume in healthy older adults and those with MCI. APOE ?4 was associated with hippocampal and amygdala volume in those with AD and MCI but was not associated in healthy older adults. No associations were found in young adults. Genetic risk for AD affects the hippocampus before the clinical symptoms of AD, reflecting a neurodegenerative effect before clinical manifestations in older adults.

SUBMITTER: Lupton MK

PROVIDER: S-EPMC4883003 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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The effect of increased genetic risk for Alzheimer's disease on hippocampal and amygdala volume.

Lupton Michelle K MK Strike Lachlan L Hansell Narelle K NK Wen Wei W Mather Karen A KA Armstrong Nicola J NJ Thalamuthu Anbupalam A McMahon Katie L KL de Zubicaray Greig I GI Assareh Amelia A AA Simmons Andrew A Proitsi Petroula P Powell John F JF Montgomery Grant W GW Hibar Derrek P DP Westman Eric E Tsolaki Magda M Kloszewska Iwona I Soininen Hilkka H Mecocci Patrizia P Velas Bruno B Lovestone Simon S Brodaty Henry H Ames David D Trollor Julian N JN Martin Nicholas G NG Thompson Paul M PM Sachdev Perminder S PS Wright Margaret J MJ

Neurobiology of aging 20160111

Reduction in hippocampal and amygdala volume measured via structural magnetic resonance imaging is an early marker of Alzheimer's disease (AD). Whether genetic risk factors for AD exert an effect on these subcortical structures independent of clinical status has not been fully investigated. We examine whether increased genetic risk for AD influences hippocampal and amygdala volumes in case-control and population cohorts at different ages, in 1674 older (aged >53 years; 17% AD, 39% mild cognitive ...[more]

PMID: 26973105

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Project description:The aim of this study was to explore the association between genetically predicted circulating levels of immunity and inflammation, and the risk of Alzheimer's disease (AD) and hippocampal volume, by conducting a two-sample Mendelian Randomization Study. We identified 12 markers of immune cells and derived ratios (platelet count, eosinophil count, neutrophil count, basophil count, monocyte count, lymphocyte count, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, CD4 count, CD8 count, CD4-to-CD8 ratio, and CD56) and 5 signaling molecules (IL-6, fibrinogen, CRP, and Lp-PLA2 activity and mass) as primary exposures of interest. Other genetically available immune biomarkers with a weaker a priori link to AD were considered secondary exposures. Associations with AD were evaluated in The International Genomics of Alzheimer's Project (IGAP) GWAS dataset (21,982 cases; 41,944 controls of European ancestry). For hippocampal volume, we extracted data from a GWAS meta-analysis on 33,536 participants of European ancestry. None of the primary or secondary exposures showed statistically significant associations with AD or with hippocampal volume following P-value correction for multiple comparisons using false discovery rate < 5% (Q-value < 0.05). CD4 count showed the strongest suggestive association with AD (odds ratio 1.32, P < 0.01, Q > 0.05). There was evidence for heterogeneity in the MR inverse variance-weighted meta-analyses as measured by Cochran Q, and weighted median and weighted mode for multiple exposures. Further cluster analyses did not reveal clusters of variants that could influence the risk factor in distinct ways. This study suggests that genetically predicted circulating biomarkers of immunity and inflammation are not associated with AD risk or hippocampal volume. Future studies should assess competing risk, explore in more depth the role of adaptive immunity in AD, in particular T cells and the CD4 subtype, and confirm these findings in other ethnicities.

Dataset Information

The effect of increased genetic risk for Alzheimer's disease on hippocampal and amygdala volume.

Publications

The effect of increased genetic risk for Alzheimer's disease on hippocampal and amygdala volume.

Similar Datasets

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