Researchers used PET scans from 4,000 people to link RBFOX1 risk variants to amyloidosis. People with lower RBFOX1 expression in their brains had more amyloid and worse cognition.
A GWAS of co-expression modules identifies a haplotype that disrupts lysosomes and myelination. ApoE4 and Aβ regulate the same module.
Alector’s AL002c antibody mobilizes microglia, reduces neuronal dystrophy, and restores normal behavior—all in mice. The clinical version is in Phase 1.
A mouse study claims that the small GTPase restrains pro-inflammatory responses in microglia. Aβ oligomers inhibit RhoA, promoting Aβ deposition and neurodegeneration.
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.
Autopsy data confirm that current tau PET tracers are unsuitable for some primary tauopathies. CryoEM structures help researchers find new ligands for tau and α-synuclein.
At the HAI 2020 conference, the tracers PI-2620 and APN-1607 appeared to bind frontotemporal dementia tau. MK-6240 looked highly sensitive. And JNJ-067 and SNFT-1 are two new kids in town.
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?
At the at Tau2020 conference, scientists show high-resolution cryoEM of α-synuclein. Two different types of fibril are composed of asymmetric protofibril units.
Post-translational modifications differ from those in AD tau fibrils, and may dictate tau strains.
The first ever cryoEM structures of Aβ fibrils extracted from AD tissue look quite different than prior structures of fibrils generated in vitro. For starters, they are right-hand twisted, not left-hand.
The protease suppresses Aβ in Down’s syndrome organoids.
Cognitive enrichment in early life correlated with less Alzheimer’s pathology, and slower cognitive decline, in late life.
Sex-specific polygenic hazard scores predict pathology and cognitive decline.
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.