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.
Live imaging of mouse brain reveals that microglia quickly engulf cell bodies while astrocytes dispose of the neuron’s more distal reaches. The cleanup crew tires with age.
In a conditional mouse knockout, lack of neuronal BIN1 slowed excitatory signaling, leading to spatial memory problems. Could this play a role in Alzheimer’s?
Loss-of-function variants in the demethylase TET2 raise a person’s risk for early and late-onset Alzheimer’s, as well as FTD and ALS, suggesting a common mechanism.
In seven papers, researchers presented a dazzling set of findings gleaned from 125,748 exomes and 15,708 genomes housed in a new database. Tidbits emerge on tau, LRRK2, and other proteins implicated in neurodegeneration.
As mice age, a busy receptor-mediated protein transport across the barrier wanes; inhibiting an alkaline phosphatase restores it. Meanwhile, the aging barrier becomes generally leaky to large molecules.
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.