Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
Homocysteine, neurodegenerative biomarkers, and APOE ε4 in neurodegenerative diseases.
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Lin William Z, Yu Di, Xiong Lisa Y, Zebarth Julia, Wang Ruoding, Fischer Corinne E, Rajji Tarek K, Tang-Wai David F, Tartaglia Carmela, Saposnik Gustavo, Swartz Richard H, Grimes David A, Lang Anthony E, Hegele Robert A, Farhan Sali, Ramirez Joel, Symons Sean, Goubran Maged, Binns Malcolm A, Lou Wendy, Dixon Roger A, Orange Joseph B, Roberts Angela C, Troyer Angela K, Zetterberg Henrik, Herrmann Nathan, Rabin Jennifer S, MacIntosh Bradley J, Masellis Mario, Lanctôt Krista L, Black Sandra E, Swardfager Walter, ONDRI Investigators
Аннотация
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.
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.