Genetic influence of plasma homocysteine on Alzheimer's disease

NEUROBIOLOGY OF AGING

卷:62

Article

Roostaei, Tina^1,2,3,4  Felsky, Daniel^3,4  Nazeri, Arash^1,2,5  De Jager, Philip L.^3,4  Schneider, Julie A.^6,7,8  Bennett, David A.^6,7  Voineskos, Aristotle N.^1,2,9 

[1] Ctr Addict & Mental Hlth, Campbell Family Mental Hlth Res Inst, Res Imaging Ctr, Kimel Family Translat Imaging Genet Lab, 250 Coll St, Toronto, ON M5T 1R8, Canada

[2] Univ Toronto, Dept Psychiat, Toronto, ON, Canada

[3] Broad Inst, Cell Circuits Program, Cambridge, MA USA

[4] Columbia Univ, Med Ctr, Dept Neurol, Ctr Translat & Computat Neuroimmunol, New York, NY USA

[5] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA

[6] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA

[7] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA

[8] Rush Univ, Med Ctr, Dept Pathol, Chicago, IL 60612 USA

[9] Ctr Addict & Mental Hlth, Underserved Populat Program, Toronto, ON, Canada

关键词: Mendelian randomization;    Alzheimer's disease;    Aging;    Plasma homocysteine;    Causal association;    Polygenic score;   

DOI  :  10.1016/j.neurobiolaging.2017.09.033

来源: Elsevier

【 摘 要 】

Observational studies have consistently reported elevated plasma homocysteine as a risk factor for Alzheimer's disease (AD). However, results from clinical trials of homocysteine-lowering treatments are inconsistent. This discrepancy may be explained by a lack of causal association between homocysteine and AD. Mendelian randomization studies have the potential to provide insight into the causality of this association through studying the effect of genetic predisposition to high homocysteine on AD. Our analyses using summarized (n = 54,162) and individual participant (n = 6987) data from Caucasian participants did not show an effect of plasma homocysteine genetic risk on susceptibility to AD. Although with smaller sample sizes, further subanalyses also did not support an effect of genetically determined plasma homocysteine on cognitive impairment and decline, beta-amyloid and tau pathology and gray matter atrophy in AD. However, we found associations with tau tangle burden (n = 251) and gray matter atrophy (n = 605) in cognitively normal elderly. Our results do not support a causal association between elevated homocysteine and risk, severity, and progression of AD. However, the relationship between genetically determined homocysteine and brain pathology in cognitively normal elderly requires further exploration. (C) 2017 Elsevier Inc. All rights reserved.

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