BACKGROUND/ OBJECTIVE: The relationship between plasma homocysteine (Hcy) levels and Alzheimer's disease (AD) has been studied for many years, but remains controversial. While a recent meta-analysis of epidemiological studies, which included observational studies, indicated that homocysteine may be a risk factor for AD, there remains a need to further demonstrate this link due to the large degree of heterogeneity between studies. Epidemiological studies have certain limitations, as their results can be affected by confounding factors and reverse causation. In this study, we evaluated the relationship between plasma homocysteine and AD by using a Mendelian randomization method to avoid problems of confounding bias and reverse causality. METHODS: We searched the PubMed and EMBASE databases for reports regarding the MTHFR C677T polymorphism (rs1801133) from the time of their inception to September 2015. These reports were combined with related observational studies, and used to evaluate the effect of MTHFR C677T (rs1801133) on the risk for AD. A recent meta-analysis of genome-wide association studies had previously suggested a relationship between homocysteine and MTHFR C677T (rs 1801133). RESULTS: Our met-analysis included 34 studies with 9397 subjects, and demonstrated a significant relationship between plasma total homocysteine levels and the risk for AD (OR = 3.37; 95% CI = 1.90-5.95; p = 2.9×10-5). CONCLUSION: Our meta-analysis demonstrated a causal link between plasma total homocysteine and the risk for AD, and provides a new insight into the etiology and prevention of AD.
BACKGROUND/ OBJECTIVE: The relationship between plasma homocysteine (Hcy) levels and Alzheimer's disease (AD) has been studied for many years, but remains controversial. While a recent meta-analysis of epidemiological studies, which included observational studies, indicated that homocysteine may be a risk factor for AD, there remains a need to further demonstrate this link due to the large degree of heterogeneity between studies. Epidemiological studies have certain limitations, as their results can be affected by confounding factors and reverse causation. In this study, we evaluated the relationship between plasma homocysteine and AD by using a Mendelian randomization method to avoid problems of confounding bias and reverse causality. METHODS: We searched the PubMed and EMBASE databases for reports regarding the MTHFR C677T polymorphism (rs1801133) from the time of their inception to September 2015. These reports were combined with related observational studies, and used to evaluate the effect of MTHFR C677T (rs1801133) on the risk for AD. A recent meta-analysis of genome-wide association studies had previously suggested a relationship between homocysteine and MTHFR C677T (rs 1801133). RESULTS: Our met-analysis included 34 studies with 9397 subjects, and demonstrated a significant relationship between plasma total homocysteine levels and the risk for AD (OR = 3.37; 95% CI = 1.90-5.95; p = 2.9×10-5). CONCLUSION: Our meta-analysis demonstrated a causal link between plasma total homocysteine and the risk for AD, and provides a new insight into the etiology and prevention of AD.
Authors: Tina Roostaei; Daniel Felsky; Arash Nazeri; Philip L De Jager; Julie A Schneider; David A Bennett; Aristotle N Voineskos Journal: Neurobiol Aging Date: 2017-10-13 Impact factor: 4.673
Authors: Seu Ping Guiraud; Ivan Montoliu; Laeticia Da Silva; Loïc Dayon; Antonio Núñez Galindo; John Corthésy; Martin Kussmann; Francois-Pierre Martin Journal: Anal Bioanal Chem Date: 2016-10-18 Impact factor: 4.142
Authors: Rebecca Carnegie; Jie Zheng; Hannah M Sallis; Hannah J Jones; Kaitlin H Wade; Jonathan Evans; Stan Zammit; Marcus R Munafò; Richard M Martin Journal: Lancet Psychiatry Date: 2019-11-20 Impact factor: 27.083