RBFOX1 Gene Tied to Amyloidosis in Preclinical Alzheimer’s
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.
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TMEM106B Variants Regulate Gene Modules, TDP-43 Pathology
A GWAS of co-expression modules identifies a haplotype that disrupts lysosomes and myelination. ApoE4 and Aβ regulate the same module.
In Mice, Activating TREM2 Tempers Plaque Toxicity, not Load
Alector’s AL002c antibody mobilizes microglia, reduces neuronal dystrophy, and restores normal behavior—all in mice. The clinical version is in Phase 1.
Does RhoA Rein in Microglial Madness?
A mouse study claims that the small GTPase restrains pro-inflammatory responses in microglia. Aβ oligomers inhibit RhoA, promoting Aβ deposition and neurodegeneration.
Too Phatal: How Microglia, Astrocytes Snuff Out Dying Neurons
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.
Primary Tauopathies Get New PET Ligands
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.
Tau PET: The Field Expands Rapidly
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.
Tau: Why Alzheimer’s Worsens Fast in Some, Slowly in Others
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?
Behold the First Human α-Synuclein CryoEM Fibril Structure
At the at Tau2020 conference, scientists show high-resolution cryoEM of α-synuclein. Two different types of fibril are composed of asymmetric protofibril units.
CryoEM of CBD Tau Suggests Another Unique Protofibril
Post-translational modifications differ from those in AD tau fibrils, and may dictate tau strains.
Right Turn: Aβ Fibril Structure from Alzheimer’s Brain Reveals Surprising Twist
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.
Can BACE2 Protect Against Amyloidosis?
The protease suppresses Aβ in Down’s syndrome organoids.
Does a Stimulating Childhood Stem Amyloid Plaques in Golden Years?
Cognitive enrichment in early life correlated with less Alzheimer’s pathology, and slower cognitive decline, in late life.
Women and Men Differ in Their Genetic Risk for Alzheimer’s Progression
Sex-specific polygenic hazard scores predict pathology and cognitive decline.
Blood-Brain Barrier Surprise: Proteins Flood into Young Brain
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.
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