Not All Bad: Phosphorylated α-Synuclein Modulates Neurotransmission
Besides accumulating in Lewy bodies, p-S129syn binds its synaptic vesicle protein partners better than does its unmodified counterpart.
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In Nasu-Hakola Disease, DAP12-Deficient Microglia Kick Repair into Overdrive
The first study to survey the brain transcriptomes of people with NHD identified microglia and astrocytes in the midst of overzealous injury repair, and narrowing blood vessels.
Did Dementia Patient Care Go Downhill During the COVID Pandemic?
Data from six countries showed an increase in prescriptions for antipsychotic drugs in 2020, with use remaining high in many countries ever since.
Droplets in the Bucket? Introducing en Masse Single-Synapse RNA-Seq
A new method reveals distinct synaptic states, as well as amyloidosis-associated changes not seen in nuclear transcriptomic data.
No Accelerated Approval for Donanemab
The FDA turned down Eli Lilly’s application based on insufficient safety data, with fewer than 100 people on the drug for one year.
Ferried Into Brain, TREM2 Antibody Stirs Microglia
A transferrin receptor binding domain helps transport the antibody across the blood-brain barrier. In the brain, it roused microglia and boosted glucose metabolism.
Cryo-EM Resolves Two Aβ40 Fibril Structures Amplified from People with CAA
In one, the N-terminus was highly structured. In the other, the N-terminus was disordered, similar to Aβ peptides found in the brain parenchyma.
Does Double-Stranded RNA From Jumping Genes Mediate Tau Toxicity?
In fly tauopathy model, dsRNA triggers inflammation and neuron death. In Alzheimer’s, dsRNA accumulates in the brain.
2022 Was Good to Basic Research, Too
Last year saw major advances in multi-omics analyses using human tissues, better animal models, deeper functional studies of gene variants, dissections of neuroimmune cell biology, and more.
2022, a Year in Review
Therapeutics research in the field ended on high hopes that lecanemab’s Phase 3 data would carry this anti-Aβ antibody to regulatory approval in country after country in 2023. This wave drew power from progress in biomarker research; but alas, much work remains to be done.
Meddling Microbiome Worsens Tauopathy and Neurodegeneration
Sex and ApoE genotype influenced the function of the millions of microbes that colonize the mouse gut. Short-chain fatty acids appear to carry messages from bacteria to cytokine-producing cells.
And Then There Were Four: A New Meningeal Membrane Discovered
The lymphatic-like membrane blankets blood vessels in the subarachnoid space and harbors immune cells.
U.S. FDA Gives Green Light to Leqembi, aka Lecanemab
Eisai’s anti-amyloid antibody got the nod via the accelerated approval pathway; the company is expected to apply for traditional approval within days.
Should People on Blood Thinners Forego Leqembi?
Recent reports of three deaths in the lecanemab extension study suggest that blood thinners, lecanemab, and cerebral amyloid angiopathy could be a dangerous combination.
Healthy, Drug-Resistant Microglia Reinvigorate Mouse Brain
Courtesy of one changed amino acid, human microglia resist drugs that typically destroy them. The cells behave normally and replenish endogenous mouse microglia
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