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

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

Evgenia Salta  1 , Orly Lazarov  2 , Carlos P Fitzsimons  3 , Rudolph Tanzi  4 , Paul J Lucassen  5 , Se Hoon Choi  6
Affiliations
Review

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

Evgenia Salta et al. Cell Stem Cell. .

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.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Figures

Figure 1.
Figure 1.. Disruption of homeostasis at the hippocampal neurogenic niche in Alzheimer’s disease: putative cellular and molecular correlates.
AD pathology, as reflected in the accumulation of amyloid plaques and neurofibrillary tangles and the loss of neurons in the neurogenic niche of the dentate gyrus, impacts distinct niche-resident cellular populations and inter-cellular signaling pathways. Captions with question marks indicate observations that have not been directly validated in AD. DGC, dentate gyrus granule cells; RGL, radial glia-like adult neural stem cells; NPC, neural precursor cells; ImN, immature neurons; aDGC, adult-born granule cells; InN, interneurons; NFT, neurofibrillary tangles.
Figure 2.
Figure 2.. Adult hippocampal neurogenesis in Alzheimer’s disease: open questions.
Remaining issues to address in order to ‘map’ the potential role of AHN in healthy (human) brain and in AD pathology, and to identify AHN-specific signatures of resilience or vulnerability to disease. Missing mechanistic insights will help assess the therapeutic relevance and the potential of recruiting AHN in to ‘rejuvenate’ the hippocampal network and boost memory in AD. SGZ, subgranular zone; GCL, granular cell layer; RG-like NSCs, radial glia-like neural stem cells.
See this image and copyright information in PMC

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