Abstract
INTRODUCTION
Elevated plasma homocysteine (Hcy) is associated with an increased risk of developing neurodegenerative diseases; however, its relationship with the apolipoprotein E (APOE) ε4 allele has not been well characterized.
METHODS
Participants clinically diagnosed with Alzheimer’s disease or mild cognitive impairment (AD/MCI), frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease were stratified by the presence of the APOE ε4 allele. Volumetric magnetic resonance imaging, plasma amyloid/tau/neurodegeneration biomarkers, and cognitive performance were quantified.
RESULTS
Across all diagnostic groups, Hcy was associated with lower brain parenchymal fraction and greater neurofilament light chain in APOE ε4 non-carriers only. In AD/MCI, Hcy was associated with phosphorylated tau 217 in APOE ε4 non-carriers, but not in carriers. Exploratory analyses revealed interactions between Hcy and APOE ε4 on memory and visuospatial function.
DISCUSSION
Hcy may contribute to neurodegeneration depending on the presence of the APOE ε4 allele and specific disease processes. Trials on vitamin B12 supplementation may consider stratifying by APOE genotype.
Highlights
Homocysteine (Hcy) was associated with neurodegenerative biomarkers across disease groups.
Relationships with Hcy were predominantly found in apolipoprotein E (APOE) ε4 non-carriers.
In Alzheimer’s disease, associations between Hcy and phosphorylated tau 217 were found in APOE ε4 non-carriers only.
Significant interactions existed between Hcy and APOE ε4 status on cognition.
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This post is Copyright: William Z. Lin,
Di Yu,
Lisa Y. Xiong,
Julia Zebarth,
Ruoding Wang,
Corinne E. Fischer,
Tarek K. Rajji,
David F. Tang‐Wai,
Carmela Tartaglia,
Gustavo Saposnik,
Richard H. Swartz,
David A. Grimes,
Anthony E. Lang,
Robert A. Hegele,
Sali Farhan,
Joel Ramirez,
Sean Symons,
Maged Goubran,
Malcolm A. Binns,
Wendy Lou,
Roger A. Dixon,
Joseph B. Orange,
Angela C. Roberts,
Angela K. Troyer,
Henrik Zetterberg,
Nathan Herrmann,
Jennifer S. Rabin,
Bradley J. MacIntosh,
Mario Masellis,
Krista L. Lanctôt,
Sandra E. Black,
Walter Swardfager,
the ONDRI Investigators,
Rick Swartz,
Mario Masellis,
Doug Munoz,
Angela Roberts,
Malcolm Binns,
Bill McIlroy,
Sandra Black,
Elizabeth Finger,
Manuel Montero‐Odasso,
Stephen Arnott,
Wendy Hatch,
Chris Hudson,
Carmela Tartaglia,
Anthony Lang,
Morris Freedman,
Lorne Zinman,
Rob Bartha,
Sean Symons,
Rob Hegele,
Paula McLaughlin | November 19, 2024