Do Overloaded Microglia Smother Stressed Neurons?
In mice with prion disease, microglia shifted from gobbling up misfolded protein to engulfing flagging neurons. This change coincided with symptom onset.
In mice with prion disease, microglia shifted from gobbling up misfolded protein to engulfing flagging neurons. This change coincided with symptom onset.
The adaptive nature of the interface between blood and brain led some scientists to envision it more like an actively managed border crossing, not a wall.
With genetic tinkering to their antibody transport vehicle, Denali scientists aim to temper both ARIA and anemia, while maintaining potency against Aβ.
Brain regions that have most recently evolved may be most vulnerable to FTLD.
In tauopathy mice, a peptide construct recruited protein phosphatase 1 to tau. Dephosphorylation lowered total tau, restoring synaptic density and memory.
In mouse brain, mRNA methylation distinguishes cell subtypes and changes with age. One standout: APP. It loses its methyls over time.
Three new papers report these myelin-producing cells contribute up to a third of plaque Aβ in transgenic mice.
A CSF proteomics study in ADAD mutation carriers identified 137 potential markers. They span the AD continuum. For 12 of them, their concentrations change prior to those of classic AD biomarkers.
Scientists are honing transferrin receptors to whisk bulky, anti-Aβ antibodies throughout the brain without setting off ARIA and anemia. By halving the effector function of their antibody transport vehicle, Denali researchers blunted red blood cell loss and vascular inflammation, without compromising engagement with Aβ plaques. In a related review, scientists propose rethinking the blood-brain barrier as more a bustling border crossing than a static wall. Read the two-part series.
Three independent studies report that these cells contribute up to a third of plaque in mouse models of amyloidosis. What’s more, suppressing oligodendrocyte Aβ production curbed neuronal hyperactivity. In human brain, too, oligodendrocytes express all the necessary genes to make Aβ peptides, hinting that the cells may play a hitherto unrecognized role in Alzheimer’s pathogenesis.
Where in the amyloid cascade does inflammation fit? Everywhere, according to a new snRNA-Seq study of more than 400 postmortem brains. The authors identified one microglial subtype that promotes plaques, another that promotes tangles, and an astrocyte subtype that contributes to cognitive decline. Intriguingly, in brains with plaques but few tangles, a different set of glial subtypes predominated. The data add to the evidence that AD has a cellular phase.
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