Second-Generation γ-Secretase Modulator Heads to Phase 2
In a Phase 1 trial of Roche’s RG6289, both plasma and CSF Aβ37 climbed, while Aβ42 fell.
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'Runner Plasma' Jogs Neurogenesis, Quells Neuroinflammation in Mice
Sedentary mice infused with the plasma of active ones had more newborn neurons in the brain and less neuroinflammation. Exercising upped plasma clusterin in mice and in humans.
Ridding Microglia of a MicroRNA Compacts Amyloid, Protects Synapses
In mice with amyloidosis, removal of miR-155 from microglia rendered the cells more receptive to IFN-γ stimulation, improving neuroprotection.
Tauopathy Transcriptomes Tell Tantalizing Tales
A comparative snRNA-Seq study of three regions from AD, PSP, and FTD brains identifies subtypes of neurons and glia hit hard in each disorder.
APOE Christchurch Variant Tames Tangles and Gliosis in Mice
Whether expressing two copies of APOE3 or -E4 with this variant, mice had less tauopathy, gliosis, atrophy. One copy of Christchurch partially protected.
Does One Copy of the Christchurch ApoE Variant Slow Alzheimer’s?
Twelve people heterozygous for this protective variant were still sharp seven years after their expected age of AD onset. One had fewer tangles than expected.
And Then There Were Five: CSF Proteomics Defines Alzheimer’s Subtypes
Each associates with distinct AD risk variants, brain atrophy, and disease severity.
Attack From Within: How Ancient Viruses Resurface to Spread Tau
Envelope proteins from endogenous retroviruses help shuttle tau seeds between cells. Could HERVs fuel tauopathies?
PLCγ2 Variants Toggle Microglial Plaque Compactors
In a mouse amyloidosis model, a protective variant tightened the reins on plaques and spared synapses; a risk variant did the opposite.
Easing Microglial Brakes Alleviates Amyloid Pathology in Mice
An antibody against the inhibitory receptor LILRB4 prevented its binding to ApoE. The upshot? Microglia engulfed more Aβ fibrils and plaque load fell.
Diabetes Drug Improves Parkinson’s Motor Symptoms in Small Trial
Motor symptoms slightly improved in 31 patients taking exenatide for 48 weeks, while the placebo group worsened. The effect persisted three months after treatment stopped.
Skin Deep: Punch Biopsies Detect Synucleinopathies
In a small sample set, phosphorylated α-synuclein was detected in the dermis of four such disorders.
TauRx Parses Subgroups to Make the Case for Methylene Blue Derivative, Again
Based on exploratory endpoints and post hoc analyses, TauRx claims HMTM benefits a subgroup of participants with MCI. Trialists are unconvinced.
Two Paths for TREM2-Positive Microglia: DAM or Senescence?
Scientists find the senescent subtype has a distinct protein signature, but little change in gene expression, causing it to be overlooked in transcriptomic studies.
Viral Vector Targets Transferrin Receptor to Deliver GBA1 to Brain
An adeno-associated virus that binds the transferrin receptor delivered β-glucocerebrosidase throughout the mouse brain.
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