Adult hippocampal neurogenesis in Alzheimer's disease: A roadmap to clinical relevance

Evgenia Salta; Orly Lazarov; Carlos P Fitzsimons; Rudolph Tanzi; Paul J Lucassen; Se Hoon Choi

doi:10.1016/j.stem.2023.01.002

Adult hippocampal neurogenesis in Alzheimer's disease: A roadmap to clinical relevance

Cell Stem Cell. 2023 Feb 2;30(2):120-136. doi: 10.1016/j.stem.2023.01.002.

Authors

Evgenia Salta¹, Orly Lazarov², Carlos P Fitzsimons³, Rudolph Tanzi⁴, Paul J Lucassen⁵, Se Hoon Choi⁶

Affiliations

¹ Laboratory of Neurogenesis and Neurodegeneration, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands.
² Department of Anatomy and Cell Biology, College of Medicine, The University of Illinois at Chicago, 808 S Wood St., Chicago, IL 60612, USA.
³ Brain Plasticity group, Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, The Netherlands.
⁴ Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, McCance Center for Brain Health, 114 16th Street, Boston, MA 02129, USA. Electronic address: tanzi@helix.mgh.harvard.edu.
⁵ Brain Plasticity group, Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, The Netherlands; Center for Urban Mental Health, University of Amsterdam, Kruislaan 404, 1098 SM, Amsterdam, The Netherlands. Electronic address: p.j.lucassen@uva.nl.
⁶ Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, McCance Center for Brain Health, 114 16th Street, Boston, MA 02129, USA. Electronic address: choi.sehoon@mgh.harvard.edu.

Abstract

Adult hippocampal neurogenesis (AHN) drops sharply during early stages of Alzheimer's disease (AD), via unknown mechanisms, and correlates with cognitive status in AD patients. Understanding AHN regulation in AD could provide a framework for innovative pharmacological interventions. We here combine molecular, behavioral, and clinical data and critically discuss the multicellular complexity of the AHN niche in relation to AD pathophysiology. We further present a roadmap toward a better understanding of the role of AHN in AD by probing the promises and caveats of the latest technological advancements in the field and addressing the conceptual and methodological challenges ahead.

Keywords: Alzheimer’s disease; adult hippocampal neurogenesis; cellular complexity; cognition; human; memory; niche; resilience; therapy.

Publication types

Review
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Adult
Alzheimer Disease*
Clinical Relevance
Cognition
Hippocampus
Humans
Neurogenesis / physiology

Abstract

Publication types

MeSH terms

Grants and funding