In mouse models of tauopathy, microglia populations are far from binary. Different activation stages emerge at different phases of disease, some marked by viral defense pathways.
Two cohorts—IDEAS and WHIMS—show Aβ accumulation and brain shrinkage in cognitively normal and impaired elderly who were exposed to levels of air pollution even within current EPA limits.
In mice, forebrain neurons with hobbled retromers ooze fragments of tau and several BACE1 substrates into the CSF. Similar proteins are up in CSF from people with MCI and Alzheimer’s disease.
Researchers found that bits of tau from the protein’s microtubule-binding region can be detected in the cerebrospinal fluid. These, not phospho-tau or total tau, reflect neurofibrillary tangles in the Alzheimer’s brain.
Breaking familiar gene-disease patterns, HTT trinucleotide expansions lead to huntingtin aggregates in prefrontal cortex. Noncoding caveolin 1 variants suppress its expression.
This astrocytic glycoprotein greases glial phagocytosis and reduces plaque burden in mice. The circadian clock protein Bmal1 suppresses it.
The enzyme degrades anti-inflammatory fatty acids in the brain. Blocking it with a brain-penetrant small molecule calmed A1 astrocytes, synapse-eating microglia, and improved amyloidosis and cognition in a mouse model.
Among a growing number of blood-based tauopathy markers, this new immunoassay may offer a way to catch preclinical disease just before symptoms show up.
Confronting unprecedented challenges this past year, scientists found ways to tide their research over and keep clinical trials mostly on track.
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.