Evidence of Wnt/beta-catenin alterations in brain and bone of a tauopathy mouse model of Alzheimer's disease.

Title

Evidence of Wnt/beta-catenin alterations in brain and bone of a tauopathy mouse model of Alzheimer's disease.

Creator

Dengler-Crish Christine M; Ball Hope C; Lin Li; Novak Kimberly M; Cooper Lisa Noelle

Publisher

Neurobiology of aging

Date

2018
2018-07

Description

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-beta 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/beta-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/beta-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.

Subject

*Alzheimer's disease; *Beta catenin; *Bone mineral density; *Neurodegeneration; *Tauopathy; *Wnt proteins; *Wnt Signaling Pathway; Alzheimer Disease/*genetics/*metabolism; Animal; Animals; beta Catenin/metabolism; Bone and Bones/*metabolism; Bone Density; Bone Remodeling/genetics; Brain/*metabolism; Disease Models; Female; Gene Expression; Male; Mice; Osteogenesis/genetics; Osteoporosis/etiology/genetics; tau Proteins/*metabolism; Tauopathies/genetics/*metabolism; Wnt Proteins/metabolism

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

148–158

Volume

67

Citation

Dengler-Crish Christine M; Ball Hope C; Lin Li; Novak Kimberly M; Cooper Lisa Noelle, “Evidence of Wnt/beta-catenin alterations in brain and bone of a tauopathy mouse model of Alzheimer's disease.,” NEOMED Bibliography Database, accessed January 20, 2021, https://neomed.omeka.net/items/show/3723.

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