Overview
- Researchers at the Buck Institute and UCSF, publishing in Advanced Science, report that APOE4 reduces bone quality in female mice through changes that standard scans cannot see and that can appear by midlife.
- In humanized mice carrying APOE2, APOE3, or APOE4, the APOE4 variant drove stronger protein and gene shifts in bone than in the hippocampus, with the clearest effects in females.
- The team traced the deficit to suppressed perilacunar and canalicular remodeling, the routine work osteocytes do to clear and rebuild tiny channels that keep bone strong.
- Proteomic surveys showed aged mouse bone, especially osteocytes, was rich in neurological proteins such as APOE and amyloid precursor protein, with osteocyte APOE levels higher in older females.
- The authors suggest osteocytes could act as early sentinels and potential treatment targets for women who carry APOE4, though the findings are preclinical and not yet proven in humans.