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.
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Oligodendrocytes Pump Out Aβ42, Worsening Plaques and Synaptotoxicity
Three new papers report these myelin-producing cells contribute up to a third of plaque Aβ in transgenic mice.
CSF Proteins Spot Alzheimer’s Mutation Carriers Decades Before Symptoms
A CSF proteomics study in ADAD mutation carriers identified 137 potential markers. They span the AD continuum. For 12 of them, their concentrations change prior to those of classic AD biomarkers.
New Alzheimer’s Gene? Cytochrome P450 Protein Linked to Tangles
In a tau PET GWAS, a SNP linked to higher expression of the oxidizing enzyme was associated with more cortical tangles.
Synaptic Skirmish: Aβ and Tau Pathologies Battle Over Brain Rhythms
Plaques rev up neural oscillations, while tangles turn them down, ultimately leading to sluggish synapses. The slowdown foreshadows symptoms.
Glial Cell Communities Conspire to Drive Alzheimer’s Disease
Transcriptomes of more than 400 postmortem brains reveal microglia and astrocyte subtypes that collaborate to precipitate pathologic changes.
X-Chromosome-Wide Association Data Spot Alzheimer’s Loci
XWAS from three research groups identified a dozen genetic loci that may help explain sex differences in AD.
Human Cell Models Reveal Two Sides to α-Synuclein Inclusions
Dynamic, lipid-rich inclusions of α-synuclein appear toxic, while stable, fibril-rich aggregates seem to protect neurons.
Put a RING on It: Targeting Intracellular Tau Aggregates for Destruction
A new strategy, which marries nanobodies or misfolded tau to a ubiquitin ligase RING domain, tags tangles for disposal.
MODEL-AD Probably Has Something for You
The consortium has cranked out dozens of mouse models of late-onset AD for the research community. Strains carry humanized Aβ and tau, and a growing list of risk variants.
Damage to the Gut Mucosa May Almost Double Parkinson's Risk
A retrospective study finds that gut damage precedes Parkinson’s disease onset, independent of bacterial infection.
Could “Big Tau” Protect Brain Regions from Tangles?
This super-sized isoform resists phosphorylation and aggregation, and occurs in cerebellum and brainstem, regions largely spared from tau pathology.
A Country Doctor, But Oh So Much More: Francisco Lopera, 73
The indefatigable Colombian neurologist leaves behind a legacy of Alzheimer’s prevention research, which, at the time of his passing, stands on the cusp of success.
Nix Tryptophan Metabolite, Temper Alzheimer’s?
Kynurenine curbs lactate production in astrocytes, which then fail to nourish neurons. Shutting down kynurenine production rescued cognition in AD mouse models.
CSF Proteomics Hints at How ApoE4 Promotes AD, and How a Drug Hinders It
Pathways of autophagy, ubiquitination, endocytosis, and glycolysis changed in Alzheimer’s. Treatment with the drug atomoxetine normalized some of them.
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