Bone derived SCLEROSTIN associated with Alzheimer´s Disease

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and the primary cause of cognitive decline among older adults (1). In 2019, 55 million people were estimated to have dementia across the world, a figure predicted to increase to 139 million by 2050 according to the WHO (2).

Advancing age is a significant risk factor for both osteoporosis and Alzheimer’s disease (AD) as individuals with osteoporosis are more susceptible to developing AD later in life (3). Recent research has uncovered a connection between Alzheimer’s disease (AD) and osteoporosis (OP), emphasizing overlapping pathological characteristics that suggest they may share common regulatory and pathogenic mechanisms (4). It has been suggested that bone tissue can influence the function of other organs through the secretion of various proteins into the bloodstream (5).  Brain and bone tissues can regulate each other in different manners through bone-brain axis (3).

Bone derived SCLEROSTIN is associated with Alzheimer´s Disease

Alzheimer’s disease and Wnt Signaling

The Wnt signaling pathway plays a critical role in embryonic development and adult tissue homeostasis. This pathway also is vital in brain development and maintenance. Studies have shown that in AD, Wnt signaling is often dysregulated, and its deficiency can contribute to synaptic degeneration and cognitive decline (6, 7). 

Alzheimer’s disease and Sclerostin

Sclerostin (SOST) is a protein secreted by osteocytes, bone cells embedded in the bone tissue. Sclerostin is a key inhibitor of Wnt/β-catenin signaling. Increased sclerostin levels, often observed with aging, are linked to a higher accumulation of amyloid-beta (Aβ) and cognitive decline in both Alzheimer’s disease patients and older adults (8). In a mouse model researchers also demonstrated that osteocyte-derived sclerostin crosses the blood–brain barrier of old mice, where it dysregulates Wnt–β-catenin signalling (9).

Proposed Mechanism

Sclerostin’s inhibition of Wnt/β-catenin signaling can lead to increased BACE1 activity, which is involved in the production of Aβ, a key protein that forms plaques in the brains of AD patients (10). 

Therapeutic Implications

Understanding the role of sclerostin in AD has led to the exploration of strategies to target the Wnt pathway or sclerostin itself, potentially as a therapeutic approach for AD (9). 

Sclerostin ELISA, #BI-20492 developed and manufactured by BIOMEDICA

• TRUSTED – most referenced Sclerostin ELISA (+320 citations)
• LOW sample volume – 20µl sample /well
•  
• For SERUM & PLASMA samples
• RELIABLE – validated  following international quality guidelines

 

 

Also available:

 Bioactive Sclerostin ELISA, BI-20472

• CHARACTERIZED ANTIBODIES – targeting the receptor binding region
• EXTENSIVELY validated for clinical samples
• LOW sample volume – 20µl sample /well 

 

Literature

1. Worlds Alzheimer´s Report 2024 , Alzheimer’s Disease International. 2024. World Alzheimer Report 2024: Global changes in attitudes to dementia. London, England: Alzheimer’s Disease International.
2. Ageing and Health, World Health Organization.
3. Research progress in Alzheimer’s disease and bone-brain axis. Zhang F, Zhang W. Ageing Res Rev. 2024 Jul;98:102341. doi: 10.1016/j.arr.2024.102341. Epub 2024 May 15. PMID: 38759893.
4. The potential link between the development of Alzheimer’s disease and osteoporosis. Nasme F, Behera J, Tyagi P, Debnath N, Falcone JC, Tyagi N. Biogerontology. 2025 Jan 20;26(1):43. doi: 10.1007/s10522-024-10181-z. PMID: 39832071; PMCID: PMC12087362.
5. Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells. Florencio-Silva R, Sasso GR, Sasso-Cerri E, Simões MJ, Cerri PS. Biomed Res Int. 2015;2015:421746. doi: 10.1155/2015/421746. Epub 2015 Jul 13. PMID: 26247020; PMCID: PMC4515490.
6. The role of Wnt signaling in the development of Alzheimer’s disease: a potential therapeutic target? Biomed Res Int. 2014;2014:301575. Wan W, Xia S, Kalionis B, Liu L, Li Y. doi: 10.1155/2014/301575. Epub 2014 May 4. PMID: 24883305; PMCID: PMC4026919.
7. Wnt Signaling Deregulation in the Aging and Alzheimer’s Brain. Front Cell Neurosci. Palomer E, Buechler J, Salinas PC. 2019 May 22;13:227. doi: 10.3389/fncel.2019.00227. PMID: 31191253; PMCID: PMC6538920.
8. Elevated plasma sclerostin is associated with high brain amyloid-β load in cognitively normal older adults. Yuan J, Pedrini S, Thota R, Doecke J, Chatterjee P, Sohrabi HR, Teunissen CE, Verberk IMW, Stoops E, Vanderstichele H, Meloni BP, Mitchell C, Rainey-Smith S, Goozee K, Tai ACP, Ashton N, Zetterberg H, Blennow K, Gao J, Liu D, Mastaglia F, Inderjeeth C, Zheng M, Martins RN. NPJ Aging. 2023 Sep 4;9(1):17. doi: 10.1038/s41514-023-00114-4. PMID: 37666862; PMCID: PMC10477312.
9. Osteocyte-derived sclerostin impairs cognitive function during ageing and Alzheimer’s disease progression. Shi T, Shen S, Shi Y, Wang Q, Zhang G, Lin J, Chen J, Bai F, Zhang L, Wang Y, Gong W, Shao X, Chen G, Yan W, Chen X, Ma Y, Zheng L, Qin J, Lu K, Liu N, Xu Y, Shi YS, Jiang Q, Guo B. Nat Metab. 2024 Mar;6(3):531-549. doi: 10.1038/s42255-024-00989-x. Epub 2024 Feb 26. PMID: 38409606.
10. The Alzheimer’s disease beta-secretase enzyme, BACE1. Cole SL, Vassar R. Mol Neurodegener. 2007 Nov 15;2:22. doi: 10.1186/1750-1326-2-22. PMID: 18005427; PMCID: PMC2211305.
11. Inhibition of Wnt signaling induces amyloidogenic processing of amyloid precursor protein and the production and aggregation of Amyloid-beta (Abeta)42 peptides. Tapia-Rojas C, Burgos PV, Inestrosa NC. J. Neurochem. 2016;139

 

Elevated plasma sclerostin is associated with high brain amyloid-β load in cognitively normal older adults. Yuan J et al., Aging. 2023.  

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.