Altered Heme and Redox Homeostasis Underpin Late-onset Alzheimer's Disease.

ABSTRACT: Early-onset Alzheimer's disease (EOAD) is associated with highly penetrant mutations in genes such as PSEN2, whereas the strongest genetic risk factor for late-onset Alzheimer's disease (LOAD) is the APOE4 allele. Despite intense research efforts, how neuronal dysfunction is initiated in LOAD cases and how the initiating events for EOAD and LOAD differ remain to be clarified. Using biochemical measurements of energy metabolism, heme and redox homeostasis, in combination with RNA-Sequencing analysis, we characterized biochemical and transcriptome differences in neurons differentiated from human EOAD and LOAD iPSC-derived neural stem cells, relative to their respective control neurons. Strikingly, we found that LOAD neurons, not EOAD neurons, are defective in heme and redox homeostasis. The

SUBMITTER: Soladogun AS 

PROVIDER: S-EPMC12435994 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature