As Mice Age, T Cells Traipse Around Their Meninges. Mayhem Ensues
Downregulation of a chemokine receptor traps T cells in the meninges. Glymph drainage slows, amyloid burden rises.
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Neurons Made from Fibroblasts Keep Imprint of Alzheimer's, Aging
Unlike iPSC-derived neurons, those created directly from fibroblasts reflect the donor's age and disease status. Epigenetic modifications appear to make the difference.
Anti-Tau Strategy PACs a Punch
Activating the G protein-coupled receptor PAC1R in the mouse brain prompts the proteasome to clear tangles.
DAMned to Death? Microglia May Proliferate to Senescence
In mice, disease-associated microglia proliferate so much that they become senescent. Plaques then run amok and synapses are lost.
How Will Aducanumab Approval Change Clinical Practice?
Physicians have a new Alzheimer’s treatment option, but most clinics are not ready to administer it. Questions remain about eligibility and insurance, to say nothing of clinician and infusion capacity.
Tau PET Best Predicts Short-Term Decline in Early Alzheimer’s
Compared to amyloid PET and cortical thickness, tau PET better foretold waning cognition across the Alzheimer's disease spectrum, from cognitively normal to dementia. Age, but not sex or APOE status, hastened deterioration over two years.
Paper Alert: pQTLs Pin GWAS Loci to Tissue Proteins, Drug Targets
Scientists linked genetic risk variants with protein changes in Alzheimer’s brain, cerebrospinal fluid, and plasma. They identified known drugs that target some of them.
Single-Cell Transcription Cum Chromatin Analysis Pins SREBF1 to AD
Single-nucleus RNA sequencing detected microglia, astrocytes, and oligodendrocytes with unique gene expression in late-stage AD brain. Where DNA at transcription factor binding sites was accessible, target gene expression rose.
More Evidence for Meningeal B Cells
B cells in the brain's dura are long-term residents that respond to inflammation.
Aducanumab: Will Appropriate-Use Recommendations Speed Uptake?
At AAIC, leading Alzheimer’s clinicians plug gaps in the FDA label. They urge exclusion of people with cerebrovascular risk, and an MRI monitoring bonanza. Meanwhile, clinical rollout starts slow, with major hospitals declining to administer.
Methylated RNA: A New Player in Tau Toxicity?
Tau oligomers ensnare an RNA-binding protein and its partner, a type of methylated RNA, in the cytosol of neurons. This triad stresses the cells, leading to neurodegeneration in mice. In people, tau draws in more methylated RNA as Alzheimer's pathology worsens.
From a Million Samples, GWAS Squeezes Out Seven New Alzheimer's Spots
This latest and largest GWAS identified 38 risk loci. The seven new ones highlight aging microglia, protein catabolism, and the LilR protein family.
In Oldest Old, Rare Longevity Variants Suppress Common Pathogenic Ones
Centenarians had nearly as many pathogenic variants as controls, but they also sported protective variants in insulin and AMPK signaling genes—longevity pathways known from animal models. Functional variants in the Wnt pathway counteracted damage from ApoE4.
ELOVL Hurts—Enzyme Makes Lipids That Turn Astrocytes Toxic
That long-sought astrocyte toxicity factor? Scientists say it's certain long-chain fatty acids. No, not the ones we get from our diet.
Viral Proteins Help Shuttle Tau Aggregates Among Cells
The SARS-CoV2 spike and other viral glycoproteins promote the transmission of proteopathic seeds carried by extracellular vesicles.
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