Peripheral metabolism of lipoprotein-amyloid beta as a risk factor for Alzheimer’s disease: potential interactive effects of APOE genotype with dietary fats

Genes & Nutrition

Review

Michael Nesbit¹  John C. L. Mamo²  Ryu Takechi²  Virginie Lam²  Mauro Vaccarezza³  Zachary J. D’Alonzo³ 

[1] Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia;Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia;Faculty of Health Sciences, School of Population Health, Curtin University, Perth, Western Australia, Australia;Faculty of Health Sciences, Curtin Medical School, Curtin University, Perth, Western Australia, Australia;Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia;

关键词: Amyloid-beta;    Lipoprotein;    Vascular;    Saturated fat;    Nutrition;    Dementia;    Genetic;    APOE;    Alzheimer’s disease;   

DOI  :  10.1186/s12263-023-00722-5

 received in 2022-09-09, accepted in 2023-02-07,  发布年份 2023

来源: Springer

【 摘 要 】

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder pathologically characterized by brain parenchymal abundance of amyloid-beta (Aβ) and the accumulation of lipofuscin material that is rich in neutral lipids. However, the mechanisms for aetiology of AD are presently not established. There is increasing evidence that metabolism of lipoprotein-Aβ in blood is associated with AD risk, via a microvascular axis that features breakdown of the blood-brain barrier, extravasation of lipoprotein-Aβ to brain parenchyme and thereafter heightened inflammation. A peripheral lipoprotein-Aβ/capillary axis for AD reconciles alternate hypotheses for a vascular, or amyloid origin of disease, with amyloidosis being probably consequential. Dietary fats may markedly influence the plasma abundance of lipoprotein-Aβ and by extension AD risk. Similarly, apolipoprotein E (Apo E) serves as the primary ligand by which lipoproteins are cleared from plasma via high-affinity receptors, for binding to extracellular matrices and thereafter for uptake of lipoprotein-Aβ via resident inflammatory cells. The epsilon APOE ε4 isoform, a major risk factor for AD, is associated with delayed catabolism of lipoproteins and by extension may increase AD risk due to increased exposure to circulating lipoprotein-Aβ and microvascular corruption.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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