Three amino acid substitutions in the Aβ sequence accelerate BACE cleavage of APP and ramp up Aβ production in rats and mice. The mice can serve as better controls for mutant APP knock-ins already in use.
The transcription factor NFATc2 mediates this response.
By looking for SNPs that affect how transcription factors bind DNA, researchers nominated causal genes for 30 Alzheimer’s and Parkinson’s GWAS hits.
ApoE4 does so much more strongly than the other known genes collected in a polygenic risk score.
Poor coordination among grid cells in the entorhinal cortex and place cells in the hippocampus compromises navigation. Grid cells fail first.
In a mouse model of ALS, removing mutant SOD1 from peripheral myeloid cells relieved neuroinflammation and extended lifespan.
Simple lifestyle factors such as alcohol consumption and stool quality alter gut flora. Research on the microbiome and disease should account for those factors, a study reports.
The panel considered the evidence for efficacy to be weak, and was troubled by too-close collaboration between the sponsor and the FDA.
The anti-Aβ biologic will be put to the test in two stages of preclinical Alzheimer’s, designated by amyloid load. The long-dormant “est” PET tracer, NAV4694, is on board to make sensitive measurements.
At CTAD, a Phase 2 open-label extension of this anti- Aβ protofibril antibody posted data as expected, and new Phase 3 trials for people with early and preclinical Alzheimer’s were described.
After years of building an online registry, designing selection algorithms, and getting sites up and running, COVID-19 nearly derailed this trial-ready cohort once again. Now, the first participants have reached the final queue.
In mice, accumulation of tau in hilar astrocytes of the dentate gyrus spells trouble for the hippocampus and for spatial memory.
Remote assessments on a smartphone closely matched tests taken in the clinic. They also may detect slip-ups in learning—an earlier cognitive deficit that arises in preclinical AD.
After missing primary endpoints in Alzheimer’s trials, this p38 MAPKa inhibitor gained some traction in a test in people with DLB.
A new single-nucleus RNA-Seq study of 3,900 endothelial cells finds a boost in angiogenesis and antigen presentation genes, drawing attention to the vascular component of AD.