4.5 Article

Cerebrovascular alterations in NAFLD: Is it increasing our risk of Alzheimer's disease?

Journal

ANALYTICAL BIOCHEMISTRY
Volume 636, Issue -, Pages -

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ab.2021.114387

Keywords

Non-alcoholic fatty liver disease; Cerebrovascular; Cerebral blood flow; Alzheimer's disease; Glymphatic system; Neuroimaging

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Non-alcoholic fatty liver disease (NAFLD) has been linked to Alzheimer's disease (AD) through shared genes and pathological mechanisms, with changes in vasculature, cerebral perfusion, and waste clearance potentially serving as key connections between the two diseases in addition to traditional factors.
Non-alcoholic fatty liver disease (NAFLD) is a multisystem disease, which has been classified as an emerging epidemic not only confined to liver-related morbidity and mortality. It is also becoming apparent that NAFLD is associated with moderate cerebral dysfunction and cognitive decline. A possible link between NAFLD and Alzheimer's disease (AD) has only recently been proposed due to the multiple shared genes and pathological mechanisms contributing to the development of these conditions. Although AD is a progressive neurodegenerative disease, the exact pathophysiological mechanism remains ambiguous and similarly to NAFLD, currently available pharmacological therapies have mostly failed in clinical trials. In addition to the usual suspects (inflammation, oxidative stress, blood-brain barrier alterations and ageing) that could contribute to the NAFLD-induced development and progression of AD, changes in the vasculature, cerebral perfusion and waste clearance could be the missing link between these two diseases. Here, we review the most recent literature linking NAFLD and AD, focusing on cerebrovascular alterations and the brain's clearance system as risk factors involved in the development and progression of AD, with the aim of promoting further research using neuroimaging techniques and new mechanism-based therapeutic interventions.

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