Cited by 161Neurogenesis and neuroplasticity mechanismsAlzheimer's disease research and treatmentsMemory and Neural Mechanisms

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Alzheimer’s disease and hippocampal adult neurogenesis; exploring shared mechanisms

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Hollands, Carolyn, Bartolotti, Nancy, Lazarov, Orly·2016·Frontiers in Neuroscience

DOI 10.3389/fnins.2016.00178PMC PMC4853383

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Abstract

New neurons incorporate into the granular cell layer of the dentate gyrus throughout life. Neurogenesis is modulated by behavior and plays a major role in hippocampal plasticity. Along with older mature neurons, new neurons structure the dentate gyrus, and determine its function. Recent data suggest that the level of hippocampal neurogenesis is substantial in the human brain, suggesting that neurogenesis may have important implications for human cognition. In support of that, impaired neurogenesis compromises hippocampal function and plays a role in cognitive deficits in Alzheimer's disease mouse models. We review current work suggesting that neuronal differentiation is defective in Alzheimer's disease, leading to dysfunction of the dentate gyrus. Additionally, alterations in critical signals regulating neurogenesis, such as presenilin-1, Notch 1, soluble amyloid precursor protein, CREB, and β-catenin underlie dysfunctional neurogenesis in Alzheimer's disease. Lastly, we discuss the detectability of neurogenesis in the live mouse and human brain, as well as the therapeutic implications of enhancing neurogenesis for the treatment of cognitive deficits and Alzheimer's disease.

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Figure 1 Common mechanisms of neurogenesis and Alzheimer's disease and the implications for learning. (A) Signals that play a role in neurogenesis, such as Notch-1, Wnt/β-catenin, CREB, sAPP, tau, and presenilin-1 are implicated in Alzheimer's disease. (B) Following learning, changes in the neurogenic niche include alterations in Notch and sAPP, increased expression of neurotrophins such as VEGF, BDNF, and IGF which enhance angiogenesis and provide support for the neurogenic niche and lead to increased neurogenesis. Upregulation of CREB signaling by neural progenitor cells and neurons may promote survival and maturation of NPCs. Increased dendritic branching of mature neurons and synaptic plasticity may be mediated by presenilin-1 and APP. The factors mediating these processes are dysfunctional or compromised in Alzheimer's disease, suggesting that defective neurogenesis may affect hippocampal function in Alzheimer's disease.CC BY · PubMed Central

Figure 2 Therapeutic and translational potential of neurogenesis. Examples of current and prospective methods for the modulation and detection of neurogenesis. Means of enhancing neurogenesis include noninvasive, environmental modulations like cognitively complex activities and exercise, as well as molecular interventions like anti-depressants, pro-neurogenic small molecules, hormones or neurotransmitters, or other manipulations of the neurogenic pathways. While readouts of human neurogenesis are typically done in postmortem tissue using radioactive isotopes or analysis of neurogeneic cell markers, imaging techniques such as fMRI, or blood biomarkers will offer non-invasive avenues to determine neurogenesis during life.CC BY · PubMed Central

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Authors: Hollands, C., Bartolotti, N., & Lazarov, O.
Affiliations: University of Illinois Chicago (US)
Corresponding author: Lazarov, Orly
ORCID: Hollands, Carolyn
Bartolotti, Nancy
Lazarov, Orly
Venue: Frontiers in Neuroscience
Publisher: Frontiers Media SA
Published: 2016-05-03
Volume: 10
Pages: 178-178
ISSN: 1662-453X (ISSN-L)
DOI: 10.3389/fnins.2016.00178
PMC: PMC4853383
OpenAlex: W2346727851
Semantic Scholar: 39dbd75fcd997404fa79a28cdaa96b3e22410e2e
Cited by: 160
References: 109
Citations by year: 2026: 1 · 2025: 8 · 2024: 12 · 2023: 11 · 2022: 9 · 2021: 13 · 2020: 31 · 2019: 26 · 2018: 29 · 2017: 18 · 2016: 2
FWCI: 3.11
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Frontiers in Neuroscience (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institute on Aging (R01AG033570, 1RC1AG036208-01 ARR)
U.S. Department of Defense (10917352)
Center for Clinical and Translational Science, University of Illinois at Chicago (CCTS-0512-06)
Topics: Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: Alzheimer's disease, adult hippocampal neurogenesis, dentate gyrus, neuronal differentiation, presenilin 1, Notch1 signaling, CREB, β-catenin, hippocampal plasticity, cognitive impairment

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Alzheimer’s disease and hippocampal adult neurogenesis; exploring shared mechanisms

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