Evidence of Wnt/β-catenin alterations in brain and bone of a tauopathy mouse model of Alzheimer's disease
Abstract
Low bone mineral density (BMD) is a significant comorbidity in Alzheimer's disease (AD) and may reflect systemic regulatory pathway dysfunction. Low BMD has been identified in several AD mouse models selective for amyloid-β or tau pathology, but these deficits were attributed to diverse mechanisms. In this study, we identified common pathophysiological mechanisms accounting for bone loss and neurodegeneration in the htau mouse, a tauopathy model with an early low BMD phenotype. We investigated the Wnt/β-catenin pathway-a cellular signaling cascade linked to both bone loss and neuropathology. We showed that low BMD persisted in male htau mice aged from 6 to 14 months, remaining significantly lower than tau-null and C57BL/6J controls. Osteogenic gene expression in female and male htau mice was markedly reduced from controls, indicating impaired bone remodeling. In both the bone and brain, htau mice showed alterations in Wnt/β-catenin signaling genes suggestive of increased inhibition of this pathway. These findings implicate dysfunctional Wnt signaling as a potential target for addressing bone loss in AD.
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Reduced bone mineral density traits are exhibited in various transgenic mouse models designed to mimic humanized AD neuropathology.
“Similar to this clinical comorbidity, reduced bone mineral density traits are exhibited in various transgenic mouse models designed to mimic humanized AD neuropathology30,31.”
From Serum amyloid P secreted by bone marrow adipocytes drives skeletal amyloidosis (2025) · cites this paper as [30]
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- Authors
- Dengler-Crish, C. M., Ball, H. C., Lin, L., Novak, K. M., & Cooper, L. N.
- Affiliations
- Northeast Ohio Medical University (US)
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 67
- Pages
- 148-158
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2789667624
- Cited by
- 58
- References
- 0
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 10 · 2023: 13 · 2022: 5 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 1
- FWCI
- 2.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- Alzheimer's disease, tauopathy, Wnt/β-catenin signaling, osteopenia, bone loss, osteogenic gene expression, bone remodeling, neurodegeneration, amyloid-beta
- MeSH terms
- Alzheimer Disease, Animals, Bone and Bones, Brain, Disease Models, Animal, Female, Male, Osteogenesis, Osteoporosis, Bone Density, Gene Expression, Bone Remodeling, tau Proteins, Tauopathies, Wnt Proteins, beta Catenin, Mice, Wnt Signaling Pathway
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