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Neuronal Stem Cells from Late-Onset Alzheimer Patients Show Altered Regulation of Sirtuin 1 Depending on Apolipoprotein E Indicating Disturbed Stem Cell Plasticity.
Jung, Matthias; Jung, Juliane-Susanne; Pfeifer, Jenny; Hartmann, Carla; Ehrhardt, Toni; Abid, Chaudhry Luqman; Kintzel, Jenny; Puls, Anne; Navarrete Santos, Anne; Hollemann, Thomas; Riemann, Dagmar; Rujescu, Dan.
Affiliation
  • Jung M; Institute of Physiological Chemistry (IPC), Faculty of Medicine, Martin Luther University Halle-Wittenberg, Hollystrasse 1, 06114, Halle (Saale), Germany. matthias.jung@uk-halle.de.
  • Jung JS; Institute of Anatomy and Cell Biology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06118, Halle (Saale), Germany.
  • Pfeifer J; Institute of Physiological Chemistry (IPC), Faculty of Medicine, Martin Luther University Halle-Wittenberg, Hollystrasse 1, 06114, Halle (Saale), Germany.
  • Hartmann C; Institute of Physiological Chemistry (IPC), Faculty of Medicine, Martin Luther University Halle-Wittenberg, Hollystrasse 1, 06114, Halle (Saale), Germany.
  • Ehrhardt T; Institute of Physiological Chemistry (IPC), Faculty of Medicine, Martin Luther University Halle-Wittenberg, Hollystrasse 1, 06114, Halle (Saale), Germany.
  • Abid CL; Institute of Physiological Chemistry (IPC), Faculty of Medicine, Martin Luther University Halle-Wittenberg, Hollystrasse 1, 06114, Halle (Saale), Germany.
  • Kintzel J; Institute of Physiological Chemistry (IPC), Faculty of Medicine, Martin Luther University Halle-Wittenberg, Hollystrasse 1, 06114, Halle (Saale), Germany.
  • Puls A; Institute of Physiological Chemistry (IPC), Faculty of Medicine, Martin Luther University Halle-Wittenberg, Hollystrasse 1, 06114, Halle (Saale), Germany.
  • Navarrete Santos A; Institute of Anatomy and Cell Biology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06118, Halle (Saale), Germany.
  • Hollemann T; Institute of Physiological Chemistry (IPC), Faculty of Medicine, Martin Luther University Halle-Wittenberg, Hollystrasse 1, 06114, Halle (Saale), Germany.
  • Riemann D; Department Medical Immunology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Magdeburger Strasse 2, 06112, Halle (Saale), Germany.
  • Rujescu D; Department of Psychiatry and Psychotherapy, Division of General Psychiatry, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Mol Neurobiol ; 61(3): 1562-1579, 2024 Mar.
Article in En | MEDLINE | ID: mdl-37728850
ABSTRACT
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. Transcript and protein analysis revealed that genes were expressed differently in NSCs from late-onset AD patients, e.g., exhibiting reduced autophagy-related protein 7 (ATG7), phosphatase and tensin homolog (PTEN), and fibroblast growth factor 2 (FGF2). Since SIRT1 expression differed between APOE3 and APOE4 NSCs, the suppression of APOE function in NSCs also repressed the expression of SIRT1. However, the forced expression of APOE3 by plasmids did not recover differently expressed genes. The altered aging markers indicate decreased plasticity of NSCs. Our study provides a suitable in vitro model to investigate changes in human NSCs associated with aging, APOE4, and late-onset AD.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Alzheimer Disease Type of study: Prognostic_studies / Risk_factors_studies Limits: Humans Language: En Journal: Mol Neurobiol Journal subject: BIOLOGIA MOLECULAR / NEUROLOGIA Year: 2024 Document type: Article Affiliation country: Germany

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Alzheimer Disease Type of study: Prognostic_studies / Risk_factors_studies Limits: Humans Language: En Journal: Mol Neurobiol Journal subject: BIOLOGIA MOLECULAR / NEUROLOGIA Year: 2024 Document type: Article Affiliation country: Germany