Acting downstream of TREM2, PLCγ2 facilitates phagocytic microglial behavior such as lipid processing. PLCγ2 also acts downstream of toll-like receptors, where it can throw a switch to inflammation.
A postmortem study found that people who had more aggregation-prone, hyperphosphorylated, oligomeric forms of tau in their brains also had a more aggressive form of Alzheimer’s disease during life. Will we personalize tauopathy care like cancer care?
Cognitive enrichment in early life correlated with less Alzheimer’s pathology, and slower cognitive decline, in late life.
Data shown at AAT-AD/PD explain why the DIAN-TU trial missed its primary endpoint. But gantenerumab strongly reduced plaques, tau, phospho-tau, and slowed NfL. This result prompted an open-label extension, sustaining hope for efficacy.
Hippocampal imaging and fluid markers of BBB damage found in ApoE4 carriers.
When these tiny mural cells carried APOE4, they secreted more ApoE, causing Aβ to deposit in capillary walls. Blocking ApoE production prevented angiopathy.
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.
According to a structural analysis, fluorescently tagged tau fragments cannot form paired helical filaments. This suggests the assay does not measure prion-like propagation.
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.
In nonhuman primates, three classes of LRRK2 kinase inhibitor cause microscopic changes in lung morphology, but they are reversible and do not impair breathing. Parkinson’s programs remain on track.
A large, cross-sectional study finds that RO-948 PET discriminates AD dementia from other disorders more accurately than do CSF biomarkers or MRI.
Harvard or MIT? The microbiomes of mice raised in different facilities dictated their response to C9 deficiency, including whether they died young. Do gut microbes influence ALS?
Built to cross the blood-brain barrier, the vehicle delivers therapeutic antibodies, enzymes, and potentially small molecules such as oligonucleotides.