At a Keystone meeting, researchers agreed that ApoE stokes damaging neuroinflammation in response to tau pathology. The E4 allele ramped up cholesterol biosynthesis in microglia and astrocytes, and even promoted neuronal damage when expressed outside of the brain.
At Keystone, the work of several groups painted TREM2 as a dedicated supporter of microglial function across neurodegenerative disease models, including those for ALS.
Working with human microglia is fraught with technical challenges, but that didn’t stop researchers at Keystone from sharing a flurry of data on how these cells act in neurodegenerative disease.
A Delicate Frontier: Human Microglia Focus of Attention at Keystone TREM2: Diehard Microglial Supporter, Consequences Be DAMed ApoE Has Hand in Alzheimer’s Beyond Aβ, Beyond the Brain Synaptic Tau Clangs the Dinner Bell for Hungry Microglia VCAM1: Gateway
Tiny yet mighty, small carbon structures glom onto and dissolve α-synuclein fibrils, neutralizing their toxicity in mouse models of Parkinson’s disease.
Variants in the gene cluster MS4A associate with levels of soluble TREM2 in human cerebrospinal fluid. MS4A encodes transmembrane receptors implicated in lipid sensing.
The proinflammatory molecule binds to Aβ oligomers and fibrils and slows nucleation in vitro, hinting it could have beneficial effects in the early stages of AD.
Get up close and personal with the GABAA receptor, a key mediator of inhibitory signaling in the brain and a drug target in a wide range of disorders, including Alzheimer’s.