Scientists at the Buck Institute for Research on Aging, together with collaborators at the University of California, San Francisco, announced on April 13 that the APOE4 gene, known as a risk factor for Alzheimer's disease, also causes bone quality deficits in female mice. The findings were published in Advanced Science.
The research highlights a previously unknown connection between genetic risk for Alzheimer's and skeletal health. This discovery could lead to earlier diagnosis of cognitive decline or new treatments for bone loss in women who carry the APOE4 gene.
Doctors have observed that people with Alzheimer's disease are more likely to suffer bone fractures and that osteoporosis in women is an early sign of possible Alzheimer's development. However, how brain and bone health are connected has not been clear until now.
The study was led by Charles Schurman, PhD. He said, "The team discovered that bone, and particularly osteocytes, the long-lived cells embedded within it, is unusually rich in proteins associated with neurological disease, including apolipoprotein E [APOE] and amyloid precursor protein." Schurman added: "Notably, APOE expression in osteocytes was twice as high in aged female mice as in young or male mice."
Using a humanized mouse model carrying different versions of the APOE gene—APOE2 (lower risk), APOE3 (neutral), or APOE4 (higher risk)—the researchers found that only females with the APOE4 variant showed strong changes at both protein and RNA levels related to bone quality. Interestingly, these changes did not show up on standard imaging scans because they affected microscopic maintenance processes inside bones rather than their shape or density.
Professor Lisa Ellerby said: "These results suggest that osteocytes could serve as early biological sentinels for age-related cognitive decline in women carrying APOE4." She added: "We think that targeting osteocyte function may open a new front in preserving bone quality in this population." Ellerby also pointed out broader implications: "While we think this work is relevant for human patients with Alzheimer's disease or with osteoporosis, this study also highlights the need for researchers to consider the human body as an entire system without isolating organs and diseases from each other."
