No Loitering: Pathogenic Liaisons Trap TDP-43 in the Cytoplasm
Methylated CAG-repeat RNAs and 14-3-3θ promote TDP-43 aggregation.
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Methylated CAG-repeat RNAs and 14-3-3θ promote TDP-43 aggregation.
A new immunoassay detects N-terminal fragments of tau. They predict tangle accumulation, cortical atrophy, and cognitive decline.
Using different methods and studying different populations, two studies report similar trajectories of fluid and imaging biomarkers over a 20-year span of AD.
In awake fruit flies, neurons pass toxic lipids to glia for storage. When the flies sleep, glia metabolize the fat to reset for a new day.
A single-nuclei RNA-Seq study found more autophagy and chaperone gene expression in familial AD brain, more intense microglial activation in sporadic.
Mitochondrial activation waned in brain cells a year before mice developed plaques. Inhibiting the kinase GSK3β partially restored the organelles.
Modeling physiological dipeptide repeat expression and partial loss of normal C9ORF72 protein, new knock-in mice show a TGF-β1-driven collagen response in their spinal neurons.
All endpoints were missed. Company to consider withdrawing the drug, as discussed during FDA Advisory Committee meeting.
ApoE2 reported as raising risk for progressive supranuclear palsy, a rare tauopathy.
Lamivudine slightly improved markers of astrogliosis and amyloid pathology. The drug suppresses activity of retrotransposons that are under-methylated in AD.
In APOE4/4 microglia, Aβ triggers an uptick of a triglyceride synthesis enzyme. The cells then accumulate lipid droplets and release something neurotoxic.
In snoozing mice, silencing neurons dampened ion waves in the interstitial fluid and slowed the flow of solutes. Activating neurons powered CSF flow through the brain.
In a multiple sclerosis model, activated microglia reverse electron transport (RET) in their mitochondria, creating oxidative stress. Blocking RET eased pathology.
O-GlcNAcase inhibitors and a vaccine head to Phase 2. New antibody strategies co-opt the proteasome to clear intracellular and extracellular tau in preclinical models.
Cerebrospinal fluid rides the pulses of cerebral arteries to enter the brain and spread into cortical tissue. This supports the existence of a human glymphatic system.