By pooling single-nucleus RNA-sequencing datasets, scientists found consistent changes across Alzheimer’s cohorts. Examples: hypermetabolic transcription, and a new neuron population that dies early on.
In this classification scheme, T, i.e. tau, means different things. Phospho-tau predicts tangle buildup, whereas tau-PET signals neurodegeneration and cognitive decline.
In human cerebral organoid cultures, mutant tau spurred astrocytes to make excess cholesterol and fatty acids. This happened before overt tau pathology.
Whether TDP-43 behaves itself in the nucleus or gets mixed up with a gelatinous blob in the cytoplasm may come down to HSPB1, which acts as TDP-43’s chief handler in the cytoplasm.
Microglial ApoE4 hobbled these cells' protective responses against Aβ and tau. In the meninges, ApoE4 made by myeloid cells slowed lymphatic drainage; at the blood-brain barrier, ApoE4 steered aging endothelial cells and pericytes toward dysregulation.
Soluble p-tau, aggregation epicenters, and gene variants emerged as potential forces that might influence how quickly tangles propagate through the brain.
In a large European study, the scans changed the diagnosis in a third of cases. They boosted the doctor's confidence in making the call, and predicted cognitive decline.
The autopsy of a woman with a the PSEN1 Paisa mutation plus a homozygous ApoE3 variant showed an unusual distribution of tau tangles. Gene-expression studies pinpointed vulnerable neurons that were spared, and riled-up microglia in tangle-ridden zones.
The I-CONECT trial found that regular video chats boosted cognition in socially isolated older people. Even a weekly phone call enhanced their feelings of social connectedness.