Roles of microglial membranes in Alzheimer's disease

Abstract

The majority of Alzheimer's disease (AD) risk genes are highly and selectively expressed by microglia in the brain. Several of these genes are related to lipid and cholesterol metabolism, lipid synthesis, lipid transport, endocytosis, exocytosis and phagocytosis. Therefore, studying the roles of cellular membrane biophysics in microglial function should improve our understanding of the AD pathology. In this chapter, we discuss how lipid rafts and membrane-cytoskeleton adhesion impact microglial-mediated oxidative stress and clearance of amyloid-β peptide (Aβ). We also discuss potential roles of lipid membrane-bound extracellular vesicles as carriers of pathological factors to promote inflammation and cytotoxicity.

Keywords: Alzheimer; Amyloid-β peptide; Caveolae; Cholesterol; Exosomes; Inflammation; Lipid rafts; Membrane-cytoskeleton adhesion; Oxidative stress; Tau.

Fig. 1

A schematic depicts Aβ induces activation of NADPH oxidase (NOX), in which the cytosolic subunits of NOX translocate to the membrane subunits located at the lipid raft. Therefore, it is reasonable to hypothesize that alterations in nano-structure and composition of lipid rafts affect NOX activation for producing superoxides.

Fig. 2

A schematic describes the role of membrane-cytoskeleton adhesion in endocytosis and exocytosis. Mechanical energy is required to overcome the membrane-cytoskeleton adhesion for detaching the membrane from cytoskeleton during the formation of invagination to produce intracellular vesicles for endocytosis and outward membrane budding for exocytosis.