The same endothelial cell response is found in various models of brain disease.
Prior research has focused on microglia interacting with synapses. New data show they also deal directly with the neuronal cell body. Like little conference rooms, specialized junctions host this communication.
In Alzheimer’s brain, granulovacuolar bodies in neurons harbor activated necrosomes. They correlate with tau pathology and neuron loss, raising new questions about how neurons die in this disease.
These cells accumulate in old mouse and human hippocampi, as well as in a mouse model of neurodegenerative disease.
At CTAD, researchers discussed possible paths forward. One option: exploring whether low doses prevent plaque accumulation while avoiding the cognitive side effects.
Specific patterns of expression defined distinct subtypes of neurons, astrocytes, oligodendrocytes, and microglia in this early affected brain region.
Cataloguing enhancer-promoter interactions in the four major cell types of the brain, researchers found that Alzheimer’s risk variants predominantly appeared in microglial enhancers.
Functional variants of AD GWAS hits found in enhancers of myeloid genes.
Loss-of-function variants in the demethylase TET2 raise a person’s risk for early and late-onset Alzheimer’s, as well as FTD and ALS, suggesting a common mechanism.
In a conditional mouse knockout, lack of neuronal BIN1 slowed excitatory signaling, leading to spatial memory problems. Could this play a role in Alzheimer’s?
In seven papers, researchers presented a dazzling set of findings gleaned from 125,748 exomes and 15,708 genomes housed in a new database. Tidbits emerge on tau, LRRK2, and other proteins implicated in neurodegeneration.
As mice age, a busy receptor-mediated protein transport across the barrier wanes; inhibiting an alkaline phosphatase restores it. Meanwhile, the aging barrier becomes generally leaky to large molecules.
Behold single proteins on the move: Super-resolution microscopy of living cells suggests the infamous protease does not form complexes with other secretases in the plasma membrane—in mouse fibroblasts, that is.
New evidence suggests the dimers impede clearance of glutamate from synapses, contributing to the hyperexcitability seen early in Alzheimer’s disease.
The phenotype of ApoE4 astrocytes and microglia resembles that of these cells in Alzheimer’s brain. Could defects in lipid metabolism and the extracellular matrix bring on the disease?