Tau, Speckle Wrecker, Disrupts the Nuclear Home
Disruption of the membraneless organelles may explain toxicity of tau aggregates.
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Disruption of the membraneless organelles may explain toxicity of tau aggregates.
Certain neurons crank up ApoE expression with age in mice. Ditto with AD progression in people. These same neurons ramp up immune response genes. The shift could foreshadow their demise.
In the plaque-ridden mouse brain, microglia that had taken up Aβ activated a unique gene-expression profile. It faded after microglia were moved to plaque-free environs.
The APP/PS1 double knock-ins begin to deposit amyloid in the brain by 3 months of age.
In mice, an IgG4 version of semorinemab better protected neurons, but for AX004, an IgG1 version better cleared tau. How to make the choice?
In the negative Phase 2 trial of prasinezumab, populations with more rapid decline benefited; this informed the design of a new Phase 2b study.
Data from Phase 3 trials of elenbecestat show no harm to cognition, leaving open a chance that the drugs could be used safely in the future.
In postmortem brain, proteins involved in all manner of vesicular functions waxed or waned with increasing phases of disease, starting years prior to symptoms.
The iPSC Neurodegenerative Disease Initiative is creating 100+ isogenic cell lines. Each carries a different risk variant for Alzheimer's or a related dementia. Scientists around the world can obtain the cells through Jackson Labs.
The first detailed look at expression profiles in blood vessels of the human brain identifies new cell subtypes. These cells express 30 of the top 45 AD risk genes.
Downregulation of a chemokine receptor traps T cells in the meninges. Glymph drainage slows, amyloid burden rises.
Unlike iPSC-derived neurons, those created directly from fibroblasts reflect the donor's age and disease status. Epigenetic modifications appear to make the difference.
Activating the G protein-coupled receptor PAC1R in the mouse brain prompts the proteasome to clear tangles.
In early stage trials, light and sound promoted neuronal communication, calmed immune cells, and slowed brain atrophy, but cognitive benefit remains unclear.
Researchers envision p-tau-based blood tests for Alzheimer’s disease within a few years, but maybe not a stand-alone test.