Via recently discovered channels, freshly made monocytes and B cells in the bone marrow of the skull and vertebrae travel directly into the meninges, where they stand ready to infiltrate the brain. These immune cells are distinct from their blood-borne counterparts.
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?
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.
Among people with early AD, the monoclonal antibody wiped out Aβ plaques and slowed cognitive and functional decline by a third, relative to placebo.
Disruption of the membraneless organelles may explain toxicity of tau aggregates.
The APP/PS1 double knock-ins begin to deposit amyloid in the brain by 3 months of age.
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.
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.
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.
Sex-specific polygenic hazard scores predict pathology and cognitive decline.
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.