Establishing bone tissue level changes associated with cognitive impairment

Alzheimer's disease (AD) and osteoporosis are common chronic conditions of aging. Although several studies have reported an association between the 2 conditions, there is limited information on tissue-level mechanisms. In the current study, we performed unbiased proteomics on thoracic vertebral samples collected from female participants enrolled in the religious orders study (ROS) and Rush Memory and Aging Project (MAP) cohorts to assess bone tissue-level changes associated with AD and other dementia-associated neuropathologies. Cognitive functioning and other participant characteristics were collected as part of ROSMAP study visits. Post-mortem evaluations assessed the burden of β-amyloid and paired helical filament tau (PHFtau) tangles, and other common age-related neuropathologies. A total of 45 bone samples were utilized from 19 female participants with a clinical diagnosis of AD dementia and 26 without AD dementia. The association between bone tissue protein abundance and cognition measured proximate to death, as well as neuropathologic indices, were evaluated using linear regression or logistic regression models, as appropriate. Bone tissue abundance of minichromosomal maintenance protein 3 (MCM3) and ubiquitin carboxyl-terminal hydrolase 24 (USP24) were positively associated with cognition and negatively associated with PHFtau tangle density. MCMC3 was also associated with cerebral arteriosclerosis, while USP24 was associated with cerebral amyloid angiopathy. Our findings suggest that processes regulating bone cell division may be involved in the link between brain and bone aging in a relationship that may not be specific to AD.