Synapses, Microglia, and Lipids in Alzheimer's Disease

Patrick J Paasila; Jason A Aramideh; Greg T Sutherland; Manuel B Graeber

doi:10.3389/fnins.2021.778822

Synapses, Microglia, and Lipids in Alzheimer's Disease

Front Neurosci. 2022 Jan 12:15:778822. doi: 10.3389/fnins.2021.778822. eCollection 2021.

Authors

Patrick J Paasila^{1

2}, Jason A Aramideh³, Greg T Sutherland¹, Manuel B Graeber³

Affiliations

¹ Charles Perkins Centre, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia.
² School of Medicine, Western Sydney University, Campbelltown, NSW, Australia.
³ Brain and Mind Centre, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia.

Abstract

Alzheimer's disease (AD) is characterised by synaptic dysfunction accompanied by the microscopically visible accumulation of pathological protein deposits and cellular dystrophy involving both neurons and glia. Late-stage AD shows pronounced loss of synapses and neurons across several differentially affected brain regions. Recent studies of advanced AD using post-mortem brain samples have demonstrated the direct involvement of microglia in synaptic changes. Variants of the Apolipoprotein E and Triggering Receptors Expressed on Myeloid Cells gene represent important determinants of microglial activity but also of lipid metabolism in cells of the central nervous system. Here we review evidence that may help to explain how abnormal lipid metabolism, microglial activation, and synaptic pathophysiology are inter-related in AD.

Keywords: APOE; Alzheimer’s disease; TREM2; lipids; microglia; synapses.

Publication types

Review