Diabetes Drug Shows Promise for Parkinson’s Disease
In a small Phase 2 trial, the GLP-1 analogue lixisenatide stabilized motor abilities over one year in people with early PD.
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Autopsies Confirm That PI-2620 Binds 4R Tau Deposits
Scientists correlated the PET signal in PSP patients with tau deposits in postmortem brain; the signal arises from neurons and oligodendrocytes.
Nuclear RNA-Binding Proteins Clump in Synucleinopathies
When the nuclear RNA-binding proteins NONO and SFPQ accumulate, adenosine-to-inosine editing of RNA runs amok. This spoils transcripts for axonal, synaptic, and mitochondrial proteins.
Enter Aη: Alternative APP Cleavage Creates Synaptotoxic Peptide
The fragment occurs naturally and rises after BACE inhibition, adding another layer of complexity to inhibitor therapy.
New PET Ligand Captures α-Synuclein in Parkinson’s, MSA Brains
C05-05 binds α-synuclein deposits in the mouse, marmoset, and human brain. Uptake in the PD midbrain correlated with motor symptom severity.
Lecanemab Follows Aduhelm’s Path to Accelerated Approval
Eisai/Biogen file for accelerated approval of lecanemab based on Phase 2 data. Eli Lilly likely to do the same for donanemab this year.
A Minority of Human Aβ Species are Toxic, Good Drug Targets
Better tissue extraction and Aβ assays could help identify the most toxic Aβ species and most promising immunotherapies.
A First for Proteinopathies—Heteromeric Fibrils
In people with FTLD-TDP-43 Type C, TDP-43 and annexin A11 twist into heteromeric amyloid filaments. Could there be others?
Do Rod-Shaped Microglia Dampen Hyperexcitability in ALS?
These microglia formed soon after overexpressing TDP-43 in a transgenic mouse. The cells pruned excitatory synapses, cooling circuits and extending lifespan.
Masking a Splicing Site Compensates for TDP-43 Dysfunction
Antisense oligonucleotides prevent mis-splicing of stathmin-2 when TDP-43 abandons the nucleus in human induced motor neurons or in the mouse brain.
Transcriptomics Paint Astrocytes as Source of Cognitive Resilience
In people who fended off cognitive slippage despite a hefty load of plaques and tangles, astrocytes cranked up choline and polyamine synthesis.
Is the ‘Atrophy’ of Immunotherapy Just the Dismantling of Plaque ‘Suburbia’?
Plaques and their surrounding cells and neurites occupy 6 percent of cortical volume. Their removal could account for shrinkage during amyloid immunotherapy.
Spooned by a Fold: MK-6240 Nestles Within Tau Protofilament
The second-generation PET ligand snuggles into the C-shaped protofilaments of tau fibrils extracted from an AD brain sample.
Single-Cell Methylomes Offer Clues to Aging
In mouse brain, mRNA methylation distinguishes cell subtypes and changes with age. One standout: APP. It loses its methyls over time.
Data Fabrication Ousted NIA Neuroscience Director Eliezer Masliah
The NIH removed Masliah from his post after an investigation found two publications with falsified data. At least 130 more papers with 500 co-authors face allegations.
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