While the FDA weighs aducanumab’s marketing license application, Alzheimer’s researchers agree that the agency’s own statistician correctly assessed the data as weak. Most prefer that one more trial be done.
A large multinational epidemiology study finds only small and inconsistent associations.
Overexpressing the endosomal activator in neurons not only caused those organelles to swell, but also bungled synaptic transmission, goaded hyperphosphorylation of tau, and destroyed cholinergic neurons.
The panel considered the evidence for efficacy to be weak, and was troubled by too-close collaboration between the sponsor and the FDA.
In mice, accumulation of tau in hilar astrocytes of the dentate gyrus spells trouble for the hippocampus and for spatial memory.
The brain shrinkage due to verubecestat emerged quickly but did not worsen or cause neurodegeneration. Curiously, both verubecestat and lanabecestat dulled episodic memory and boosted verbal fluency.
Researchers identified genetic variants that may explain why some ApoE4 carriers remain free of Alzheimer’s, while some ApoE2 carriers do not.
In mice lacking the recycling protein GGA3, BACE1 trafficking stalls, local Aβ production increases, and axons swell. Does this explain the neuritic dystrophies seen in early AD?
Single-cell RNA sequencing of 16,000 live microglia freshly isolated from human brain reveals nine distinct subtypes. One fades in Alzheimer’s. Why?
Quantifying 95 post-translational modifications of tau extracted from AD and control brains, a proteomics study proposes a “processive” model of phosphorylation, ubiquitination, acetylation that drive aggregation and map to distinct stages of disease.
Among people with early AD, the monoclonal antibody wiped out Aβ plaques and slowed cognitive and functional decline by a third, relative to placebo.
In a mouse model of ALS, removing mutant SOD1 from peripheral myeloid cells relieved neuroinflammation and extended lifespan.
Regulators in the U.S. and Europe have certified a mass-spectrometry-based blood test for amyloid-β. Plasma phospho-tau markers are poised to come next.
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.
ApoE4 does so much more strongly than the other known genes collected in a polygenic risk score.