Genetic variation of oxidative phosphorylation genes in stroke and Alzheimer's disease

NEUROBIOLOGY OF AGING

卷:35

Article

Biffi, Alessandro^1,2,3  Sabuncu, Mert R.^4,5  Desikan, Rahul S.⁶  Schmansky, Nick⁴  Salat, David H.^1,7  Rosand, Jonathan^1,2,3  Anderson, Christopher D.^1,2,3 

[1] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA

[2] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[3] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

[4] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA

[5] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA

[6] Univ Calif San Diego, Dept Radiol, San Diego, CA USA

[7] VA Boston Healthcare Syst, Boston, MA USA

关键词: OXPHOS;    Alzheimer's disease;    Stroke;    Mitochondria;    Genes;   

DOI  :  10.1016/j.neurobiolaging.2014.01.141

来源: Elsevier

【 摘 要 】

Previous research implicates alterations in oxidative phosphorylation (OXPHOS) in the development of Alzheimer's disease (AD). We sought to test whether genetic variants within OXPHOS genes increase the risk of AD. We first used gene-set enrichment analysis to identify associations, and then applied a previously replicated stroke genetic risk score to determine if OXPHOS genetic overlap exists between stroke and AD. Gene-set enrichment analysis identified associations between variation in OXPHOS genes and AD versus control status (p = 0.012). Conversion from cognitively normal controls to mild cognitive impairment was also associated with the OXPHOS gene-set (p = 0.045). Subset analyses demonstrated association for complex I genes (p < 0.05), but not for complexes II-V. Among neuroimaging measures, hippocampal volume and entorhinal cortex thickness were associated with OXPHOS genes (all p < 0.025). The stroke genetic risk score demonstrated association with clinical status, baseline and longitudinal imaging measures (p < 0.05). OXPHOS genetic variation influences clinical status and neuroimaging intermediates of AD. OXPHOS genetic variants associated with stroke are also linked to AD progression. Further studies are needed to explore functional consequences of these OXPHOS variants. (C) 2014 Elsevier Inc. All rights reserved.

【 授权许可】

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