Abstract

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 investigated. 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. The study enrolled participants meeting a set of screening inclusion and exclusion criteria and were stratified into Aβ− (n = 65) and Aβ+ (n = 35) according to their brain Aβ load assessed using Aβ-PET (positron emission tomography) imaging. Plasma SOST levels, apolipoprotein E gene (APOE) genotype and several putative AD blood-biomarkers including Aβ40, Aβ42, Aβ42/Aβ40, neurofilament light (NFL), glial fibrillary acidic protein (GFAP), total tau (t-tau) and phosphorylated tau (p-tau181 and p-tau231) were detected and compared. It was found that plasma SOST levels were significantly higher in the Aβ+ group (71.49 ± 25.00 pmol/L) compared with the Aβ− group (56.51 ± 22.14 pmol/L) (P < 0.01). Moreover, Spearman’s correlation analysis showed that plasma SOST concentrations were positively correlated with brain Aβ load (ρ = 0.321, P = 0.001). Importantly, plasma SOST combined with Aβ42/Aβ40 ratio significantly increased the area under the curve (AUC) when compared with using Aβ42/Aβ40 ratio alone (AUC = 0.768 vs 0.669, P = 0.027). In conclusion, plasma SOST levels are elevated in cognitively unimpaired older adults at high risk of AD and SOST could complement existing plasma biomarkers to assist in the detection of preclinical AD.

Details

Title
Elevated plasma sclerostin is associated with high brain amyloid-β load in cognitively normal older adults
Author
Yuan, Jun 1   VIAFID ORCID Logo  ; Pedrini, Steve 2 ; Thota, Rohith 3 ; Doecke, James 4   VIAFID ORCID Logo  ; Chatterjee, Pratishtha 5   VIAFID ORCID Logo  ; Sohrabi, Hamid R. 6 ; Teunissen, Charlotte E. 7 ; Verberk, Inge M. W. 7   VIAFID ORCID Logo  ; Stoops, Erik 8 ; Vanderstichele, Hugo 9 ; Meloni, Bruno P. 10 ; Mitchell, Christopher 11 ; Rainey-Smith, Stephanie 12 ; Goozee, Kathryn 13   VIAFID ORCID Logo  ; Tai, Andrew Chi Pang 1 ; Ashton, Nicholas 14 ; Zetterberg, Henrik 15 ; Blennow, Kaj 16   VIAFID ORCID Logo  ; Gao, Junjie 17 ; Liu, Delin 1 ; Mastaglia, Frank 10 ; Inderjeeth, Charles 18 ; Zheng, Minghao 1   VIAFID ORCID Logo  ; Martins, Ralph N. 19 

1  Perron Institute for Neurological and Translational Science, Nedlands, Australia (GRID:grid.482226.8) (ISNI:0000 0004 0437 5686); The University of Western Australia, Centre for Orthopaedic Translational Research, Medical School, Nedlands, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910) 
2  Edith Cowan University, School of Medical and Health Sciences, Joondalup, Australia (GRID:grid.1038.a) (ISNI:0000 0004 0389 4302) 
3  Macquarie University, Department of Biomedical Sciences, North Ryde, Australia (GRID:grid.1004.5) (ISNI:0000 0001 2158 5405) 
4  Australian E-Health Research Centre, CSIRO, Brisbane, Australia (GRID:grid.467740.6) (ISNI:0000 0004 0466 9684) 
5  Edith Cowan University, School of Medical and Health Sciences, Joondalup, Australia (GRID:grid.1038.a) (ISNI:0000 0004 0389 4302); Macquarie University, Department of Biomedical Sciences, North Ryde, Australia (GRID:grid.1004.5) (ISNI:0000 0001 2158 5405) 
6  Macquarie University, Department of Biomedical Sciences, North Ryde, Australia (GRID:grid.1004.5) (ISNI:0000 0001 2158 5405); Murdoch University, Centre for Healthy Ageing, Health Future Institute, Perth, Australia (GRID:grid.1025.6) (ISNI:0000 0004 0436 6763); Edith Cowan University, The Centre of Excellence for Alzheimer’s Disease Research and Care, Joondalup, Australia (GRID:grid.1038.a) (ISNI:0000 0004 0389 4302) 
7  Vrije Universiteit Amsterdam, Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Neurodegeneration, Amsterdam UMC, Amsterdam, The Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227) 
8  ADx NeuroSciences, Technologiepark 94, Gent, Belgium (GRID:grid.518198.c) 
9  Biomarkable BV, Gent, Belgium (GRID:grid.518198.c) 
10  Perron Institute for Neurological and Translational Science, Nedlands, Australia (GRID:grid.482226.8) (ISNI:0000 0004 0437 5686) 
11  The University of Western Australia, Centre for Orthopaedic Translational Research, Medical School, Nedlands, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910) 
12  Edith Cowan University, School of Medical and Health Sciences, Joondalup, Australia (GRID:grid.1038.a) (ISNI:0000 0004 0389 4302); Murdoch University, Centre for Healthy Ageing, Health Future Institute, Perth, Australia (GRID:grid.1025.6) (ISNI:0000 0004 0436 6763) 
13  Macquarie University, Department of Biomedical Sciences, North Ryde, Australia (GRID:grid.1004.5) (ISNI:0000 0001 2158 5405); KaRa Institute of Neurological Disease, Macquarie Park, Australia (GRID:grid.489025.2) 
14  the Sahlgrenska Academy at the University of Gothenburg, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Mölndal, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582); University of Gothenburg, Wallenberg Centre for Molecular and Translational Medicine, Mölndal, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582) 
15  the Sahlgrenska Academy at the University of Gothenburg, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Mölndal, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582); Sahlgrenska University Hospital, Clinical Neurochemistry Laboratory, Mölndal, Sweden (GRID:grid.1649.a) (ISNI:000000009445082X); UCL Institute of Neurology, Queen Square, Department of Neurodegenerative Disease, London, UK (GRID:grid.83440.3b) (ISNI:0000000121901201); UK Dementia Research Institute at UCL, London, UK (GRID:grid.83440.3b) (ISNI:0000000121901201); Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China (GRID:grid.24515.37) (ISNI:0000 0004 1937 1450) 
16  the Sahlgrenska Academy at the University of Gothenburg, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Mölndal, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582); Sahlgrenska University Hospital, Clinical Neurochemistry Laboratory, Mölndal, Sweden (GRID:grid.1649.a) (ISNI:000000009445082X) 
17  Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Department of Orthopaedic Surgery, Shanghai, China (GRID:grid.412528.8) (ISNI:0000 0004 1798 5117) 
18  The University of Western Australia, School of Medicine, Perth, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910); Sir Charles Gairdner and Osborne Park Health Care Group, Perth, Australia (GRID:grid.1012.2) 
19  Edith Cowan University, School of Medical and Health Sciences, Joondalup, Australia (GRID:grid.1038.a) (ISNI:0000 0004 0389 4302); Macquarie University, Department of Biomedical Sciences, North Ryde, Australia (GRID:grid.1004.5) (ISNI:0000 0001 2158 5405); Murdoch University, Centre for Healthy Ageing, Health Future Institute, Perth, Australia (GRID:grid.1025.6) (ISNI:0000 0004 0436 6763); Edith Cowan University, The Centre of Excellence for Alzheimer’s Disease Research and Care, Joondalup, Australia (GRID:grid.1038.a) (ISNI:0000 0004 0389 4302) 
Pages
17
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20563973
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41514-023-00114-4
ProQuest document ID
2860455346
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.