Behold single proteins on the move: Super-resolution microscopy of living cells suggests the infamous protease does not form complexes with other secretases in the plasma membrane—in mouse fibroblasts, that is.
Technical limitations may have misrepresented the transcriptional state of these cells, obscuring detection of their activation signature in frozen postmortem tissue from Alzheimer’s brain.
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?
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.
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.
Many Alzheimer’s trials had minimal dosing interruptions, but recruitment stopped for a time. Others trials fared worse, with some scrapped altogether. One administered study drug in an ambulance.
Tissue from 13-week-old fetuses carrying the huntingtin repeat expansion shows defects in neuronal polarity and proliferation, which lead to fewer neurons populating some brain regions.
Homozygous carriers of GM17—a common IgG1 variant the HSV-1 virus has evolved to evade—had quadruple the risk of developing AD. In a small Swedish cohort, that is.