Synapses, Microglia, and Lipids in Alzheimer's Disease

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.

Automated summary

Alzheimer's disease is characterized by synaptic dysfunction, pathological protein deposits, and cellular dystrophy. Recent studies have shown that microglia play a direct role in synaptic changes. Variants of certain genes are important determinants of microglial activity and lipid metabolism. This review examines the relationship between abnormal lipid metabolism, microglial activation, and synaptic pathophysiology in Alzheimer's disease.