Alzheimer's Disease Risk Factor APOE4 Exerts Dimorphic Effects on Female Bone - PubMed
5 hours ago
- #Alzheimer's disease
- #Bone fragility
- #Sex differences
- Alzheimer's disease (AD) and bone fracture risk are linked, with osteoporosis in women acting as an early predictor of AD.
- Apolipoprotein E (Apoe) was found enriched in aged mouse bone, particularly in osteocytes, with higher expression in aged female bone.
- APOE4, a human Alzheimer's risk allele, caused strong sex-specific effects on bone transcriptome and proteome in humanized knock-in mice.
- APOE4-induced proteomic disruptions were more pronounced in female bone than in the hippocampus, leading to bone fragility without altering cortical structure.
- Bone fragility in females resulted from impaired osteocyte perilacunocanalicular remodeling, highlighting APOE4 as a driver of early osteocyte dysfunction.