Lipid Droplets in Microglia Concerned in Alzheimer’s Pathology
Microglia are innate immune cells resident within the central nervous system. Microglial dysfunction is clearly a contributing issue within the onset and development of age-related neurodegenerative situations, together with Alzheimer’s illness, in addition to the accompanying persistent irritation of mind tissue. As to why microglia grow to be problematic and inflammatory, there are any variety of doable contributing mechanisms to contemplate. Mobile senescence, mitochondrial dysfunction, reactions to cell particles or the presence of persistent viral infections, and extra. On this vein, researchers right here talk about extreme lipid accumulation in microglia as a doable contributing reason behind Alzheimer’s illness.
A number of genetic threat elements for Alzheimer’s illness implicate genes concerned in lipid metabolism and plenty of of those lipid genes are extremely expressed in glial cells. Nonetheless, the connection between lipid metabolism in glia and Alzheimer’s illness pathology stays poorly understood. By means of single-nucleus RNA sequencing of mind tissue in Alzheimer’s illness, we now have recognized a microglial state outlined by the expression of the lipid droplet-associated enzyme ACSL1 with ACSL1-positive microglia being most ample in sufferers with Alzheimer’s illness having the APOE4/4 genotype.
In human induced pluripotent stem cell-derived microglia, fibrillar amyloid-β induces ACSL1 expression, triglyceride synthesis, and lipid droplet accumulation in an APOE-dependent method. Moreover, conditioned media from lipid droplet-containing microglia result in Tau phosphorylation and neurotoxicity in an APOE-dependent method. Our findings recommend a hyperlink between genetic threat elements for Alzheimer’s illness with microglial lipid droplet accumulation and neurotoxic microglia-derived elements, doubtlessly offering therapeutic methods for Alzheimer’s illness.
Hyperlink: https://doi.org/10.1038/s41586-024-07185-7
