With Aduhelm in Retrenchment, Lecanemab Completes FDA Submission
In wake of Medicare coverage decision, Biogen jettisons aducanumab sales staff but keeps trials going. Eisai/Biogen wrap up accelerated approval application to U.S. regulators.
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Sleep: Too Little, or Too Much, Foreshadows Brain Shrinkage
One of the largest studies to date links sleep problems in middle age with worse cognition and lower brain volume years later. What causes what remains unclear.
Hyperconnectivity in Cingulate Precedes Amyloid. Astrocytes to Blame?
Years before plaques develop in AD, the cingulate cortex brims with excess activity. Ditto in APP knock-in mice, where listless astrocytes allow a neuronal frenzy. Do astrocytes play into the pathological cascade this early?
Presenilin Mutations Stall Endosomal Transport, Swell Axons
In neurons lacking PS1, late endosomes get bogged down by imbalanced calcium. This puts kinases in a tizzy, slows motor proteins, and makes neurites dystrophic.
Membrane Border Patrol: Cholesterol Stymies Tau Uptake, Aggregation
Depleted of cholesterol, neurons laid out the welcome mat for tau aggregates, which readily crossed into the cytosol and seeded aggregation there. Adding cholesterol blocked entry and seeding.
Tau-PET Imaging Brings Braak Staging to Life
Using a sensitive tau-PET tracer, researchers tied neuroimaging, CSF biomarkers, and cognitive symptoms to the progression of tau pathology in AD.
Diversity: FDA Guidance and New Data on Incidence/Biomarkers by Race
The guidance may help sponsors increase racial diversity in clinical trials. Studies in U.S. veterans and other cohorts show differences in incidence, and in blood levels of tau by race.
Somatic Mutations Accrue in Alzheimer's Neurons
Excitatory neurons from people who died with Alzheimer’s disease carried more mutations than did neurons from healthy controls. Do such variants contribute to the demise of neurons?
From Near and Far, Aβ Beckons Tau to Tangle in the Cortex
Interactions with both remote and local amyloid-laden neurons drive tangles through the Alzheimer's brain. Is person-to-person variability in these interactions why patients differ in their progression?
Death by Goo: TDP-43 Gels Paralyze Proteasomes in Neurons
Cryo-electron tomography reveals amorphous blobs of TDP-43 C-terminal fragments. They ensnare stalled proteasomes in the cytosol.
Drilling Down into the CMS Aduhelm Decision—A Primer
In its national coverage determination, Medicare limits Aduhelm coverage to clinical trials, but OKs registry-based studies for traditionally approved anti-Aβ antibodies. This may change once new efficacy data comes out.
Ratio of Short to Long Aβ Peptides: Better Handle on Alzheimer's than Aβ42/40?
Low levels of Aβ37, 38, 40 reflect low processive activity of γ-secretase. They track with age at onset in people with autosomal-dominant mutations, and may track with cognitive decline in sporadic AD.
In Alzheimer's, More ZZZs Once Wakefulness Neurons Die
In people who had Alzheimer’s disease, degeneration of subcortical neurons that drive wakefulness correlated with more time asleep at night.
Is This Mutation Pathogenic? Alzforum Updates System for Making This Call
Applied to more than 500 alleles in APP, PSEN1, and PSEN2, the new classification can help scientists gauge how pathogenic, or benign, a given variant might be
DNA Nuclease Fans the Flames of Huntington’s Disease
Rare genetic variants that blunt FAN1 activity cause rapid expansion of CAG trinucleotide repeats in somatic cells.
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