Transcriptomics Paint Astrocytes as Source of Cognitive Resilience
In people who fended off cognitive slippage despite a hefty load of plaques and tangles, astrocytes cranked up choline and polyamine synthesis.
In people who fended off cognitive slippage despite a hefty load of plaques and tangles, astrocytes cranked up choline and polyamine synthesis.
The largest autopsy-confirmed study of tau PET to date finds that the scans cannot identify early Alzheimer’s disease or PART.
Synapses of fast-spiking interneurons nestle in holes within dense extracellular matrix. These ‘cages’ corral glutamate, so it won’t spark excitotoxicity.
Knocking out this immunoglobulin receptor makes microglia fit to fight. An anti-PILRA antibody does the same.
In cultured cells, mutant human tau that was forced together formed liquid droplets. When tau was missing its N-terminus, the droplets hardened into insoluble aggregates.
These microglia formed soon after overexpressing TDP-43 in a transgenic mouse. The cells pruned excitatory synapses, cooling circuits and extending lifespan.
Ratio of 3R/4R tau in extracellular vesicles identified people with behavioral variant FTD and PSP. Vesicle TDP43 identified bvFTD and ALS.
In mice, the innate immune protein slips into neurons, where it interacts with the translation machinery.
New data from cultured cells suggest tau snarling into tangles may be a stepwise process. Tau first oligomerized and condensed into liquid droplets, which remained soluble. When tau had lost its N-terminus, however, the protein solidified into beta sheets. Truncated tau is common in the aging brain, hinting this could be a key factor in vivo as well.
A survey of the transcriptomes of more than a million cells spanning six regions from 48 human brains has uncovered more pathways involved in Alzheimer’s pathogenesis. A first analysis pegged astrocytes as potential agents of resilience in people who remained sharp despite having plaques and tangles. Reelin-expressing neurons appeared vulnerable. The data will be available for more analyses.
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