FDA Advisory Committee Throws Cold Water on Aducanumab Filing
The panel considered the evidence for efficacy to be weak, and was troubled by too-close collaboration between the sponsor and the FDA.
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The panel considered the evidence for efficacy to be weak, and was troubled by too-close collaboration between the sponsor and the FDA.
In a mouse model of cortical multiple sclerosis, microglia and monocytes swooped in to gobble up synapses when dendritic calcium rose. Spines grew back once inflammation subsided.
Epidemiology study reveals 1.5-times higher risk of dementia after herpes virus infection. Short-term antiviral treatment appears to lower risk.
The first whole-genome manipulation of protein expression in neurons by CRISPR reveals a deadly chain of events. Bad processing by lysosomes leads to build-up of lipids and iron. Oxidative stress revs up. Neurons die by ferroptosis.
In therapy-like paradigm, suppressing ApoE4 in astrocytes toned down tauopathy. This assuaged microglia, neurodegeneration, and revived nest-building.
Hippocampal imaging and fluid markers of BBB damage found in ApoE4 carriers.
According to a structural analysis, fluorescently tagged tau fragments cannot form paired helical filaments. This suggests the assay does not measure prion-like propagation.
When these tiny mural cells carried APOE4, they secreted more ApoE, causing Aβ to deposit in capillary walls. Blocking ApoE production prevented angiopathy.
In mice with defective PS1 phosphorylation, microglial autophagy falters, exacerbating Aβ burden.
The first high-resolution look at LRRK2 implies that pathogenic mutations increase binding to microtubules by biasing the kinase domain toward a closed, active conformation.
A C9ORF72 polydipeptide repeat induces aggregation by direct interaction with TDP-43, while progranulin mutations that trigger microglial toxicity cause TDP-43 to accumulate via complement.
While one anti-Aβ antibody thwarts initial seeding of fibrils, and others keep fibrils from lengthening, aducanumab prevents oligomers forming on their surface. In vitro, that is.
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.