In it to Wnt it–CCrish lab identifies Wnt signaling deficits in bone and brain of Alzheimer’s model mice
Exciting research from the CCrish Lab has uncovered a potential mechanistic link between two rather unsuspecting partners: low bone mineral density (BMD) and Alzheimer’s disease (AD).
Low BMD and osteoporosis occur at twice the rate in AD patients–a relationship that is mistakenly attributed to the coincidence of aging, late-stage disease-induced immobility, or because post-menopausal women are more susceptible to either osteoporosis or AD. However, data have debunked these misconceptions, and point towards a common, unknown disease mechanism that contributes to both skeletal and brain degeneration.
In a study recently accepted for publication in the journal Neurobiology of Aging, our multidisciplinary research team of neuroscientists and skeletal biologists provide evidence of such a mechanism: deficits in canonical Wnt/β-Catenin signaling. The Wnt/β-Catenin pathway is an evolutionarily conserved intracellular signaling system that regulates critical functions in most bodily tissues–bone and brain included. Our studies focused on htau mice, a transgenic model that expresses mutant tau pathology akin to human AD. Htau mice also show early bone loss–a finding previously characterized by our lab (Dengler-Crish et al., 2017). We used dual x-ray absorptiometry (DEXA) to measure bone density across the lifespan of these mice (a technique also used in humans), and then measured gene expression associated with Wnt/β-Catenin activation in femur and tibia bones and in hippocampus and brainstem regions. Our results indicated pathological disruptions at multiple levels of Wnt signaling in both bone and brain of htau mice. These deficits were not present in non-AD control mice that experienced normal age-related bone loss.
Our findings begin to fill a major gap in understanding of how non-neural systems are affected in AD, and illuminate Wnt signaling as a possible new therapeutic target for certain presentations of the disease. We have much more work to do to determine why and when Wnt signaling is disrupted in AD, how to fix these disruptions, and how best to deploy what we learn to treating patient populations.
Notably, the CCrish Lab research team completing this work consists of a unique group of female scientists at the Northeast Ohio Medical University (NEOMED) that represent the Colleges of Medicine, Pharmacy, and Graduate Studies. NEOMED’s mission is to train the next generation of physicians, pharmacists and biomedical researchers by bringing the latest developments from our labs and the global scientific community into the classroom.
Full-text link to the final article is provided here by permission of corresponding author Dengler-Crish and copyright holder ©2018 Elsevier: