Delivery Courier? Microglia Drop Neprilysin Off Near Plaques in Brain Researchers genetically engineered human iPSC-microglia to deliver neprilysin when the cells are near amyloid plaques Both local injection and brain-wide engraftment of neprilysin-secreting microglia reduced Aβ pathology Only widespread engraftment helped reduce pathologies and improve neuronal density in the subiculum
Microglia Build Plaques to Protect the Brain - ALZFORUM Could it be that microglia build plaques rather than bust them? In the April 15 Nature Immunology, researchers led by Greg Lemke at the Salk Institute for Biological Studies, La Jolla, California, add to the evidence for this idea In a mouse model of amyloidosis, the researchers hobbled microglial
Do Rod-Shaped Microglia Dampen Hyperexcitability in ALS? Rod-shaped microglia appear in response to neuronal hyperactivity in TDP-43 mice The cells cozy up to dendrites and prune excitatory synapses Without rod-shaped microglia, hyperactivity worsens, and animals die sooner
No Mere Microglial Marker, TMEM119 Supports Aβ Phagocytosis The data indicated that microglia take up TMEM119 as they phagocytose Aβ peptides Microglial Magnet In microglial cell cultures treated with Aβ, TMEM119 (green) co-localized with LRP1 (red) and the lysosomal marker LAMP1 (white) [Courtesy of Liu et al , 2025 ] How would dearth of TMEM119 affect microglial responses?
Expunging Microglial Lipid Droplets Boosts Phagocytosis Wu and colleagues confirmed that cultured-microglia-carrying lipid droplets struggled with phagocytosis, poorly engulfing fluorescently labeled inactivated E Coli or Aβ What if microglia were free of excessive lipids? To find out, researchers targeted FIT2, a protein embedded in the endoplasmic reticulum that helps lipid droplets form and bud
After Immunotherapy, Amyloid Clearance Comes Down to Microglial Moods Microglia also took on distinct signatures depending on the extent of amyloid clearance in their neighborhood For example, in cases of extensive plaque clearance, the cells upregulated myristoylated alanine-rich C kinase substrate, a protein involved in cell motility and phagocytosis, and fibroblast growth factor receptor 3 in addition to ApoE
Could Monocyte-Derived Microglia Cause Some Cases of Parkinsonism . . . Certain brain regions of healthy old mice and humans harbor monocyte-derived microglia The transcriptome of some monocyte-derived microglia was identical to that of yolk sac-derived microglia Monocyte-derived microglia bearing a DNMT3A gene variant caused motor deficits resembling parkinsonism
Ferried Into Brain, TREM2 Antibody Stirs Microglia | ALZFORUM It drove TREM2 signaling in cultured human microglia, inducing their proliferation and enhancing their phagocytosis In a mouse model of amyloidosis, the antibody slid into the brain, increased microglial activity, and boosted brain glucose metabolism