Alzheimer’s Gene MS4A4A Governs the State of Microglia
A protective variant promotes anti-inflammatory microglia, while a risk variant depletes them.
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Those Declining Dementia Rates? It's Not the Plaques and Tangles
Across a three-decade span, there was no difference in amyloid pathology, but younger cohorts had healthier cerebrovasculature.
Secreted by Neurons, ApoE4 Makes Tangles and Degeneration Worse
In mice, nixing ApoE4 from neurons squelched tau pathology, myelin loss, and neuronal death.
Does Neural Activity Drive DNA Repair?
In mice, the neuronal transcription factor NPAS4 recruits DNA repair machinery to active promoters; without it, double-strand DNA breaks accumulate.
Gene Editing for Huntington’s Disease Shows Promise in Pigs
A single injection with CRISPR machinery suppressed mutant protein and improved gait and survival, suggesting the strategy deserves further exploration.
Putting Palmitate on Synaptotagmin-11 Stymies α-Synuclein Tetramers
The fatty acid shields Syt11 from degradation. With more of it around, α-synuclein monomers cling to membranes.
No Easy Answers on Clinical Meaningfulness of Alzheimer’s Treatments
Meaningfulness must account for the disease stage a patient is at, his or her priorities, and effects over time, researchers say.
New Stem Cell-Derived Neuron Datasets Available
Scientists turned iPSCs from people with ALS or Parkinson’s into motor neurons or dopaminergic neurons, respectively, then characterized them with a plethora of multi-omics.
Paper Alert: Plasma P-tau217 Predicts Future Cognitive Decline
Cognitively normal older adults with high levels of the biomarker slid quickly toward dementia.
Single-Nuclei Multi-omics Spots Wonky Gene Regulation
Can joint analysis of gene expression, chromatin, and transcription factors help explain how transcription changes in Alzheimer’s disease?
When Perivascular Macrophages Spew SPP1, Microglia Eat Synapses
In mice, oligomeric Aβ causes these macrophages to produce SPP1. Knocking out this pro-inflammatory cytokine quiets microglia and protects synapses.
Catch and Release: Cryo-EM Reveals How LRP2 Receptor Recycles Cargo
As it moves from the neutral pH of the cell surface to the acidic environs of the endosome, LRP2 switches its conformation from ligand receiver to dumper.
Higher-Resolution Spatial Transcriptomics Maps Mayhem Near Plaques
Microglia within 10 micrometers of Aβ plaques expressed a disease-associated signature. Astrocytes rubbernecked from a bit farther away.
Can ‘Cryptic Peptides’ Peg People with TDP-43 Pathology?
Mis-splicing events produce novel proteins that can be detected in the cerebrospinal fluid of ALS/FTD patients before their symptoms start.
The Chaperone FKBP12 Shields Tau from Aggregation
The protein binds to segments of tau that are prone to aggregate, preventing tangles and neurodegeneration.
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