APOE4 Causes Widespread Molecular and Cellular Alterations Associated with Alzheimer’s Disease Phenotypes in Human iPSC-Derived Brain Cell Types

By Yuan-Ta Lin, Jinsoo Seo, Fan Gao, Heather M. Feldman, Hsin-Lan Wen, Jay Penney, Hugh P Cam, Elizabeta Gjoneska, W. Raja, Jemmie Cheng and 11 more. Neuron, 2018

963 citations recorded by the source corpus.

(microglia-like cells). APOE4 neurons exhibited increased synapse number and elevated A b 42 secretion relative to isogenic APOE3 cells while APOE4 astrocytes displayed impaired A b uptake and cholesterol accumulation. Notably, APOE4 microglia-like cells exhibited altered morphologies, which correlated with reduced A b phagocytosis. Consistently, converting APOE4 to APOE3 in brain cell types from sAD iPSCs was sufficient to attenuate multiple AD-related pathologies. Our study establishes a reference for human cell-type-specific changes associated with the APOE4 variant.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/5cdb27e94888eb2ee1fb8cd363f37a82cb17cbe5

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Citations in the corpus

• Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020, background): “Compared to isogenic APOE3, APOE4 variants featured an increased number of synapses and elevated Aβ42 secretion in neurons, while APOE4 astrocytes showed impaired Aβ uptake and cholesterol accumulation [465].”