Single-cell RNA sequencing of 16,000 live microglia freshly isolated from human brain reveals nine distinct subtypes. One fades in Alzheimer’s. Why?
Quantifying 95 post-translational modifications of tau extracted from AD and control brains, a proteomics study proposes a “processive” model of phosphorylation, ubiquitination, acetylation that drive aggregation and map to distinct stages of disease.
Neurons take up extracellular vesicles containing tau oligomers more readily than they do free tau. Some gift: This speeds the march of tauopathy through mouse brain.
In both mice and (wo)men, the sex difference comes down to an Aβ-glutamate receptor-prion protein troika.
In cultured cells, lysosomal activity was necessary to enable tau seeds to break out of internalized exosomes and trigger the aggregation of tau in the cytosol.
This pathway may transmogrify microglia during neurodegeneration, without the help of TREM2.
The brain shrinkage due to verubecestat emerged quickly but did not worsen or cause neurodegeneration. Curiously, both verubecestat and lanabecestat dulled episodic memory and boosted verbal fluency.
Overexpressing the endosomal activator in neurons not only caused those organelles to swell, but also bungled synaptic transmission, goaded hyperphosphorylation of tau, and destroyed cholinergic neurons.
High amyloid burden and neuroinflammation, neuronal excitability, and tangles and oligodendrocyte loss distinguish the disease types.
The blood-based marker may be far more scalable and cost-effective for tracking the disease than PET imaging and CSF biomarkers.
Among people with early AD, the monoclonal antibody wiped out Aβ plaques and slowed cognitive and functional decline by a third, relative to placebo.
Topline results suggested that the anti-inflammatory treatment stabilized cognition and function over six months. The trial did not include biomarkers.
Aging macrophages and microglia poorly burn glucose and enter an inflammatory state. Revving their metabolism preserved synapses and memory in mice. What does prostaglandin have to do with it?
Researchers identified genetic variants that may explain why some ApoE4 carriers remain free of Alzheimer’s, while some ApoE2 carriers do not.
By tracing the transcriptomes of neurons that wither early and late in the course of Alzheimer’s disease, researchers peg subpopulations of excitatory neurons in entorhinal cortex as selectively vulnerable to tau. Reactive astrocytes aid and abet.