Premium
A First Report of altered bone microarchitecture in a commonly used mouse model of Alzheimer Disease (5XFAD Tg+)
Author(s) -
Suryadevara Vidyani,
Krehbiel Connor J.,
Walker Chandler L.,
Willis Monte
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.06700
Subject(s) - osteoporosis , dementia , cortical bone , medicine , pathology , disease
Alzheimer’s disease (AD) is prevalent among 44 million people worldwide and is characterized by dementia and deterioration of cognitive capabilities. An accelerated bone loss (osteoporosis) is found in the early stages of the AD and correlates to the common morbidities observed in AD patients (e.g., hip fractures). We hypothesize that primary AD disease alters the bone structure and biomedical properties through direct and indirect (e.g., systemic crosstalk) mechanisms that are currently unknown. The 5XFAD Tg+ mice are a common preclinical AD model with five human AD‐related mutations, including three mutations in human APP (KM670/671NL, I716V, APP V717I) and 2 in human PSEN1 (M146L (A>C), L286V). These mice express high levels of Aβ42 and develop amyloid pathology and cognitive deficits by around four months. In the present study, we investigated the bone microarchitecture in 10‐month‐old hemizygous 5X FADTg+ compare to age‐ and strain‐matched wildtype controls. Specifically, left femurs were assessed by using mCT (SkyScan 1172, 9 mm resolution) for cortical and trabecular properties in the distal femur metaphysis (1 mm) and mid‐diaphysis regions for trabecular and cortical regions, respectively. Analysis of the 5X FAD Tg+ MALE femur microarchitecture revealed distinct changes in the cortical regions, including a significant reduction in total cross‐sectional area, bone marrow area, cortical thickness, periosteal and endocortical surface compared to wildtype controls. In contrast, the 5X FAD Tg+ FEMALE femur cortical properties were not different from wildtype controls. No change in trabecular microarchitecture was identified in MALE or FEMALE 5X FAD Tg+ mice. The alterations in the male cortical bone marrow area potentially indicate alterations through direct crosstalk with the brain, possibly through Aβ deposition, which is present outside of the brain at ten months, which we are presently investigating. The sex‐dependent effects on bone may be due to altered gender‐related transcription factors, possibly mimicking gender‐dependent changes in Aβ deposition and impaired memory levels. Support or Funding Information Lilly Foundation/Indiana Center for Musculoskeletal Health/ IU School of Medicine, Physician Scientist Initiative, Scientific Research Initiative