The first steps of endocytosis faltered in astrocytes expressing ApoE4, but pumping in PICALM reversed the problem. A new study places two Alzheimer’s risk factors into the same cellular mechanism.
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.
Data shown at AAT-AD/PD explain why the DIAN-TU trial missed its primary endpoint. But gantenerumab strongly reduced plaques, tau, phospho-tau, and slowed NfL. This result prompted an open-label extension, sustaining hope for efficacy.
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.
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.
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.