APOE4 impacts cortical neurodevelopment and alters network formation in human brain organoids.

ABSTRACT: Apolipoprotein E4 (APOE4) is the leading genetic risk factor for Alzheimer's disease. While most studies examine the role of APOE4 in aging, APOE4 causes persistent changes in brain structure as early as infancy and is associated with altered functional connectivity that extends beyond adolescence. Here, we used human induced pluripotent stem cell-derived cortical and ganglionic eminence organoids (COs and GEOs) to examine APOE4's influence during the development of cortical excitatory and inhibitory neurons. We show that APOE4 reduces cortical neurons and increases glia by promoting gliogenic transcriptional programs. In contrast, APOE4 increases proliferation and differentiation of GABAergic progenitors resulting in early and persistent increases in GABAergic neurons. Multi-electrode arr

SUBMITTER: Meyer-Acosta KK 

PROVIDER: S-EPMC12277819 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature