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Cited by 43Alzheimer's disease research and treatmentsWnt/β-catenin signaling in development and cancerDementia and Cognitive Impairment Research

The multifaceted role of WNT signaling in Alzheimer’s disease onset and age-related progression.

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Kostes, William W., Brafman, David A.·2023·Cells
DOI 10.3390/cells12081204PMC PMC10136584
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Abstract

The evolutionary conserved WNT signaling pathway orchestrates numerous complex biological processes during development and is critical to the maintenance of tissue integrity and homeostasis in the adult. As it relates to the central nervous system, WNT signaling plays several roles as it relates to neurogenesis, synaptic formation, memory, and learning. Thus, dysfunction of this pathway is associated with multiple diseases and disorders, including several neurodegenerative disorders. Alzheimer’s disease (AD) is characterized by several pathologies, synaptic dysfunction, and cognitive decline. In this review, we will discuss the various epidemiological, clinical, and animal studies that demonstrate a precise link between aberrant WNT signaling and AD-associated pathologies. In turn, we will discuss the manner in which WNT signaling influences multiple molecular, biochemical, and cellular pathways upstream of these end-point pathologies. Finally, we will discuss how merging tools and technologies can be used to generate next generation cellular models to dissect the relationship between WNT signaling and AD.

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  • Recent work in AD cerebral organoids has highlighted Wnt pathway dysregulation as a core feature of disease progression.

    “Aberrant Wnt signaling has been implicated in Aβ production, tau phosphorylation, and synapse loss in multiple models, and recent work in AD cerebral organoids has highlighted Wnt pathway dysregulation as a core feature of disease progression (Kostes and Brafman, 2023; Tapia-Rojas and Inestrosa, 2018).”

    From Isogenic human stem cell models reveal mutation-dependent protective mechanisms of APOE3 Christchurch (2026) · cites this paper as Kostes and Brafman, 2023

    Section 6 (Conclusions; page unavailable) links WNT signaling to Aβ pathology, tau hyperphosphorylation, and synaptic loss. Section 5 (Future Trends; page unavailable) discusses hiPSC-based AD models as a way to investigate unanswered questions, but does not report cerebral-organoid work establishing WNT dysregulation as a core feature of disease progression. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Aberrant Wnt signaling has been implicated in Aβ production, tau phosphorylation, and synapse loss in multiple models.

    “Aberrant Wnt signaling has been implicated in Aβ production, tau phosphorylation, and synapse loss in multiple models, and recent work in AD cerebral organoids has highlighted Wnt pathway dysregulation as a core feature of disease progression (Kostes and Brafman, 2023; Tapia-Rojas and Inestrosa, 2018).”

    From Isogenic human stem cell models reveal mutation-dependent protective mechanisms of APOE3 Christchurch (2026) · cites this paper as Kostes and Brafman, 2023

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Sorted by citations

Authors
Kostes, W. W., & Brafman, D. A.
Affiliations
Arizona State University (US)
Corresponding author
Brafman, David A.
ORCID
Brafman, David A.
Venue
Cells
Publisher
MDPI AG
Published
2023-04-21
Volume
12
Issue
8
Pages
1204
ISSN
2073-4409 (ISSN-L)
DOI
10.3390/cells12081204
PMC
PMC10136584
OpenAlex
W4366690730
Cited by
43
References
51
Citations by year
2026: 14 · 2025: 18 · 2024: 10 · 2023: 1
FWCI
1.53
Type
journal article
Language
en
Open access
Licence
Locations
  • Cells (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health (R01GM121698, R21AG056706)
  • Alzheimer’s Association (R01GM121698, R21AG056706)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Wnt signaling, Alzheimer's disease, neurodegeneration, synaptic dysfunction, cognitive decline, age-related disease progression, neurogenesis, learning and memory, cellular disease model, animal models
MeSH terms
Alzheimer Disease, Animals, Central Nervous System, Neurogenesis, Wnt Signaling Pathway, Cognitive Dysfunction

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