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.
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.
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.
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.
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.
In mice lacking the recycling protein GGA3, BACE1 trafficking stalls, local Aβ production increases, and axons swell. Does this explain the neuritic dystrophies seen in early AD?
Regulators in the U.S. and Europe have certified a mass-spectrometry-based blood test for amyloid-β. Plasma phospho-tau markers are poised to come next.
Remote assessments on a smartphone closely matched tests taken in the clinic. They also may detect slip-ups in learning—an earlier cognitive deficit that arises in preclinical AD.