Genetic influence of plasma homocysteine on Alzheimer's disease.
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Abstract | 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. |
Year of Publication | 2018
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Journal | Neurobiol Aging
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Volume | 62
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Pages | 243.e7-243.e14
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Date Published | 2018 02
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ISSN | 1558-1497
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DOI | 10.1016/j.neurobiolaging.2017.09.033
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PubMed ID | 29102475
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PubMed Central ID | PMC6953632
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Grant list | U01 AG016976 / AG / NIA NIH HHS / United States
U24 AG021886 / AG / NIA NIH HHS / United States
503480 / MRC_ / Medical Research Council / United Kingdom
CIHR / Canada
U01 AG032984 / AG / NIA NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
082604/2/07/Z / WT_ / Wellcome Trust / United Kingdom
R01 AG033193 / AG / NIA NIH HHS / United States
R01 MH099167 / MH / NIMH NIH HHS / United States
R01 AG017917 / AG / NIA NIH HHS / United States
U01 AG024904 / AG / NIA NIH HHS / United States
P30 AG010161 / AG / NIA NIH HHS / United States
R01 MH102324 / MH / NIMH NIH HHS / United States
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