Protective AD Variant Pinpoints Sweet Spot for Microglial Activation
Phospholipase C-γ2 acts downstream of TREM2 to rev up beneficial inflammation, phagocytosis, and cell survival.
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Epoxide Hydrolase, a Fat New Target for Alzheimer’s Therapy?
The enzyme degrades anti-inflammatory fatty acids in the brain. Blocking it with a brain-penetrant small molecule calmed A1 astrocytes, synapse-eating microglia, and improved amyloidosis and cognition in a mouse model.
Chaperone Stabilizer Fends Off Amyloid, Memory Loss in Mice
A small molecule binds the retromer complex, preventing Aβ accumulation, tau hyperphosphorylation, and their downstream consequences in mice.
Toxic α-Synuclein: Egged on by ApoE4, Thwarted by ApoE2?
Quite independently of what it does to Aβ or tau, ApoE4 stokes α-synuclein pathology in mouse models. People with Lewy body dementia who carry ApoE4 had more phosphorylated synuclein in their brains, and their cognition declined faster.
Resilience Redefined: Sharp at Age 100, Still Sharp at 102
Centenarians who scored high on the MMSE stayed cognitively and physically active over the next two years, even if they carried genetic risk factors for Alzheimer’s. What protects these lucky few?
Traveling C9ORF72 Dipepides Jam Proteasomes in Neighboring Neurons
The slowdown of proteasomes stymied TDP-43’s entry into the nucleus and promoted its aggregation in the cytoplasm.
Klotho Variant Cuts ApoE4’s Alzheimer Risk by a Third
Massive meta-analysis finds the longevity gene’s VS haplotype staves off mild cognitive impairment and AD. It reduces amyloid burden.
Mouse Brain Mapped in 3D, at High Resolution
This update of the Allen Brain Institute atlas reveals detailed anatomical structures and provides a common framework for comparing brain datasets.
Massive Proteomics Studies Peg Glial Metabolism, Myelination, to AD
Separately, cerebrovascular disease drove an uptick in neurofilament light in the brain, indicating neurodegeneration.
In Colombian Alzheimer’s Kindred, Blood NfL Climbs 22 Years Before Symptoms
The plasma biomarker neurofilament light was able to distinguish individual mutation carriers from noncarriers three years prior to onset.
New Astrocyte Marker Allows Purification from Mixed Cultures
Researchers identify a way to isolate human astrocytes generated from induced pluripotent stem cells. And astrocytes stand out in FTD-prone brain areas.
Alzheimer’s Research Restarts, Cautiously
As the SARS-Cov-2 infection peak passes in some areas, scientists are resuming lab work and clinical studies, albeit with new safety protocols in place. Regions differ greatly in how fast they can reopen.
TMEM106B Variants Regulate Gene Modules, TDP-43 Pathology
A GWAS of co-expression modules identifies a haplotype that disrupts lysosomes and myelination. ApoE4 and Aβ regulate the same module.
CryoEM of CBD Tau Suggests Another Unique Protofibril
Post-translational modifications differ from those in AD tau fibrils, and may dictate tau strains.
Can BACE2 Protect Against Amyloidosis?
The protease suppresses Aβ in Down’s syndrome organoids.
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