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.
The tracer distinguished people with progressive supranuclear palsy from controls with a sensitivity of 85 percent, suggesting potential as a diagnostic for 4R tauopathies.
The findings hint at a liver-brain axis that transmits inflammation from periphery to brain, and could suggest therapeutic targets for preserving brain function.
New drug application is first for Alzheimer’s disease in the U.S. since 2003, and first based on amyloid hypothesis.
Released from hippocampal neurons in response to experience, the cytokine prompted microglia to eat extracellular matrix around synapses. This facilitated growth of new spines, and sharpened memory.
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.
Sex-specific polygenic hazard scores predict pathology and cognitive decline.
Cognitive enrichment in early life correlated with less Alzheimer’s pathology, and slower cognitive decline, in late life.
Alzforum encourages users to visit the Virtual Exhibit Hall, where companies showcase their newest initiatives, products, and services. We welcome F. Hoffmann-La Roche, joining our other exhibitors — Biogen, BioLegend, Dash Genomics, Inc., Abcam, BrainXell, and the Jackson Laboratory.
Scientists have captured unprecedented images of secretases and their substrates as they flit about the plasma membrane of cultured mouse fibroblasts. Labeling individual proteins with distinct fluorophores reveals that γ-secretase travels mostly solo, sometimes in pairs. It lingers with substrates but not with other secretases. It pauses at “hotspots” of unique lipid composition, where it seems to rest. The constructs and techniques developed for this study should help researchers study γ-secretase dynamics in neurons.
Researchers have identified another way in which exercise helps the brain. In mice that run, the liver enzyme Gpld1 rises, suppressing peripheral inflammation. Somehow, this peripheral effect boosts BDNF and neurogenesis in the brain and sharpens cognition. The data suggest the existence of a liver-brain axis, and may offer new therapeutic approaches. In people, too, Gpld1 rises with exercise.
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