biostudies-literatureJung MDeutsche ForschungsgemeinschaftMartin-Luther-Universität Halle-Wittenberg1562-1579https://www.ebi.ac.uk/biostudies/studies/S-EPMC10896791biostudies-literatureUnknown61(3)Late-onset Alzheimer's disease (AD) is a complex multifactorial disease. The greatest known risk factor for late-onset AD is the E4 allele of the apolipoprotein E (APOE), while increasing age is the greatest known non-genetic risk factor. The cell type-specific functions of neural stem cells (NSCs), in particular their stem cell plasticity, remain poorly explored in the context of AD pathology. Here, we describe a new model that employs late-onset AD patient-derived induced pluripotent stem cells (iPSCs) to generate NSCs and to examine the role played by APOE4 in the expression of aging markers such as sirtuin 1 (SIRT1) in comparison to healthy subjects carrying APOE3. The effect of aging was investigated by using iPSC-derived NSCs from old age subjects as healthy matched controls. TranscrMolecular neurobiologyNeuronal Stem Cells from Late-Onset Alzheimer Patients Show Altered Regulation of Sirtuin 1 Depending on Apolipoprotein E Indicating Disturbed Stem Cell Plasticity.PMC10896791JU 3146/3-1RTG 2155 ProMoAgeRiemann DJung JSNavarrete Santos AAbid CLKintzel JPfeifer JPuls AJung MHartmann CEhrhardt TRujescu DHollemann TfalseNeuronal Stem Cells from Late-Onset Alzheimer Patients Show Altered Regulation of Sirtuin 1 Depending on Apolipoprotein E Indicating Disturbed Stem Cell Plasticity.Late-onset Alzheimer's disease (AD) is a complex multifactorial disease. The greatest known risk factor for late-onset AD is the E4 allele of the apolipoprotein E (APOE), while increasing age is the greatest known non-genetic risk factor. The cell type-specific functions of neural stem cells (NSCs), in particular their stem cell plasticity, remain poorly explored in the context of AD pathology. Here, we describe a new model that employs late-onset AD patient-derived induced pluripotent stem cells (iPSCs) to generate NSCs and to examine the role played by APOE4 in the expression of aging markers such as sirtuin 1 (SIRT1) in comparison to healthy subjects carrying APOE3. The effect of aging was investigated by using iPSC-derived NSCs from old age subjects as healthy matched controls. Transcr2024-01-01T00:00:00Z2024 Mar2026-07-15T09:29:29.667Z2024-11-07T00:57:51.698ZS-EPMC108967913772885010.1007/s12035-023-03633-z