Translational evidence indicates APOE2 benefits longevity independent of its protective effects on Alzheimer’s disease, which preserved activity and the metabolism of apoE protein and associated-lipids would be key to understanding.
Increased excitation and decreased inhibition associated with abnormal neuronal morphology, aberrant ion channel properties, and synaptic dysfunction contribute to hyperexcitability in Alzheimer’s disease hiPSC-derived neuronal cultures and cerebral organoids.
Increased levels of brain Hebp1 starting from the presymptomatic stage of Alzheimer’s disease contributes to progressive neuronal loss by triggering mitochondrial-dependent apoptosis in neurons exposed to elevated heme.
New methods reveal that complex local splicing variations are more prevalent in animals than previously appreciated, and demonstrate that local splicing variations are relevant for studies of development, gene regulation and neurodegenerative diseases.
Somatically derived genomic mosaicism in the form of increased DNA content and APP copy number in single neurons plausibly has a function in sporadic Alzheimer’s disease and points to functions for single-neuron gene copy number changes.
Experiments in a mouse model for Alzheimer’s disease using germ-free and conventionally housed animals reveal that microbiota-derived short-chain fatty acids promote the deposition of cerebral Aβ plaques.
The APP intracellular domain (AICD) physiologically regulates synaptic GluN2B-containing NMDA receptor current, a process that could contribute to pathological Alzheimer's disease-related synaptic failure upon increase of AICD levels in adult neurons.