Oral Presentation ANZBMS-MEPSA-ANZORS 2022

Elevated bone-derived sclerostin in plasma is associated with high brain amyloid-β load in cognitively normal older adults (#251)

Jun Yuan 1 2 , Steve Pedrini 3 , Pratishtha Chatterjee 3 4 , Bruno Meloni 1 , Andrew Tai 1 2 , Junjie Gao 5 , Frank Mastaglia 1 , Charles Inderjeeth 6 , Ralph Martins 3 4 , Minghao Zheng 1 2
  1. Perron Institute for Neurological and Translational Science, Perth, Western Australia, Australia
  2. Centre for Orthopaedic and Translational Research, School of Biomedical Sciences, University of Western Australia, M Block, WA, Australia
  3. School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia
  4. Department of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia
  5. Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
  6. Department of Rehabilitation & Aged Care, Sir Charles Gairdner Hospital, Nedlands, WA, Australia

Osteoporosis and Alzheimer’s disease (AD) mainly affect older individuals, and the possibility of an underlying link contributing to their shared epidemiological features has rarely been studied. Interestingly, growing research has demonstrated that bone has endocrine-like functions by secreting various proteins that influence other body systems. In the current study, we investigated the association between levels of plasma sclerostin (SOST), a protein primarily produced by bone, and brain amyloid-beta (Aβ) load, a pathological hallmark of AD. A cohort of 100 older adults (66-89 years old) with normal global cognition (MMSE score >26) were enrolled for the study. Participants were divided into Aβ- (n = 65) and Aβ+ (n=35) groups based on their brain Aβ status assessed using positron emission tomography (PET) imaging. Plasma SOST concentrations were significantly elevated in Aβ+ participants (p = 0.003, p* = 0.008), and were positively correlated with increasing brain Aβ load (rs = 0.321, p = 0.001) before and after adjusting for covariates of age, gender and apolipoprotein E ε4 (APOE ε4) status. Furthermore, it was demonstrated that combining SOST with a base model built with AD risk factors including age, gender and APOE ε4 status had a higher diagnostic accuracy (AUC = 0.818, CI = 0.733 – 0.903) than using the base model alone (AUC = 0.787, CI = 0.693 – 0.882, p = 0.228). This study has identified a potential pathogenic association between bone and brain in older individuals, and highlights that plasma SOST levels may be associated with the pathology of AD.