Presenilin L166P Mutation, a Model of Familial Alzheimer's Disease, Leads to Early Onset Bone Loss.

ABSTRACT: Accelerated bone loss has been reported in the early stages of Alzheimer's disease (AD) as indicated by reduced bone mineral density and increased fracture risk in these patients, compared to healthy individuals. In the present study, we investigated bone loss in mouse models of familial Alzheimer's disease harboring the Presenilin 1 (L166P) knock-in mutation (PSEN1 KI), with or without the human amyloid precursor protein transgene (hAPP Tg+) known to induce brain amyloid pathology by 6 months. Female and not male 12-month PSEN1/hAPP Tg+ mice exhibited reduced whole-body bone mineral density and bone mineral content, compared to sex-matched controls. Consistent with PSEN1 L166P driving the phenotype, female PSEN1 KI mice lacking the hAPP transgene also displayed low bone mass with a reduct

SUBMITTER: Suryadevara V 

PROVIDER: S-EPMC12775720 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature