AUTHOR=Paasila Patrick J. , Aramideh Jason A. , Sutherland Greg T. , Graeber Manuel B. 

TITLE=Synapses, Microglia, and Lipids in Alzheimer’s Disease

JOURNAL=Frontiers in Neuroscience

VOLUME=15

YEAR=2022

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2021.778822

DOI=10.3389/fnins.2021.778822

ISSN=1662-453X

ABSTRACT=<p>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.</p>