Droplets of Unsaturated Fats Burden Human ApoE4 Astrocytes
Simple addition of choline, a phospholipid building block, ameliorated ApoE4-related deficiencies.
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Anti-Tau Antibody Data Leave Best Isotype Unclear
In mice, an IgG4 version of semorinemab better protected neurons, but for AX004, an IgG1 version better cleared tau. How to make the choice?
Sans C9ORF72, Microglia Devour More Aβ Plaques. Synapses, Too.
In the face of aging or amyloidosis, microglia lacking C9ORF72 ramped up interferon genes, accumulated lysosomes, and ate synapses.
ApoE4 Hastens Alzheimer’s Disease in Down’s Syndrome
In carriers of the allele, cognition falters a bit earlier than in noncarriers. Brain amyloid, structure, and metabolism changed, as previously seen in sporadic and familial AD, but only some of the fluid markers did.
Do Gene Expression Signatures of Aging Signal AD?
A subset of cognitively normal people died with an AD-like transcriptome, suggesting they may have been on the path to disease.
New Ways to Target TREM2 Beg the Question: Up or Down?
Lowering TREM2 via antisense oligos cleared plaques in mice, while antibody fragments reduced shedding of sTREM2. Best therapeutic strategy? Still hazy.
iPSC-Derived Neurons Mirror LOAD Pathologies of Their Donors
Higher Aβ42 in these neurons correlated with greater plaque load and cognitive decline in their 53 donors, suggesting amyloid overproduction in sporadic AD.
Not All Bad? APOE4 Sharpens Memory in Older People
Cognitively intact 70-year-old people carrying APOE4 recalled objects and their locations slightly better than did noncarriers. The advantage persisted even among people who had amyloid plaques.
Can an Old Diuretic Drug Disarm APOE4, Prevent Alzheimer’s?
Bumetanide normalizes molecular signatures linked to the AD risk allele. People taking the medicine may be less likely to develop Alzheimer’s.
What FDG PET ‘Sees’ in AD: Angry Microglia, Not Just Neurons
A new study reports that activated microglia soak up glucose, and may be responsible for the elevated FDG PET signal seen in early Alzheimer's disease. Mouse microglia used 28 times more FDG than did neurons.
Even In the Healthy, ApoE4 Stirs Up Trouble, Scientists Say
The AD risk allele steers microglia toward an inflammatory state long before plaques or tangles emerge.
Doubling of Tau Seeds, Not Spread, Sets Pace of Tauopathy in Alzheimer's
A paper marrying math modeling with biological data proposes that, past Braak Stage III, tau aggregates double every five years in the neocortex. By this stage, they were already distributed throughout, de-emphasizing spread.
TREM2 Risk Variant Eggs on Clique of Microglia in AD Brain
Transcriptomics pinpoints an expansion of pro-inflammatory microglia in people who carried the R47H-TREM2 variant. A similar cadre of microglia arose in female tauopathy mice carrying a single copy of the AD risk variant.
Could Targeting CD22 Restore Microglial Lysosome Trafficking?
In human microglia-like cells, soluble CD22 stalled normal breakdown of fats. Blocking sCD22 greased the system, evoking a treatment for lysosomal-storage disorders.
Deep Sleep Accelerates Synuclein Removal in Mice
Parkinson’s mice that got deeper slow-wave sleep cleared synuclein deposits, perhaps via better glymphatic function. Sleep deprivation worsened synuclein phosphorylation and aggregation.
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