Cerebrospinal Fluid Stanniocalcin-1 as a Biomarker for Alzheimer’s Disease and Other Neurodegenerative Disorders

Abstract

Stanniocalcin-1 (STC-1) is a nerve cell-enriched protein involved in intracellular calcium homeostasis regulation. Changes in calcium regulation are hypothesized to play a role in the pathophysiology of Alzheimer's disease (AD). The expression of STC-1 increases in response to ischemic stroke, but whether it is altered in neurodegenerative disorder, particularly Alzheimer's disease (AD), has not been investigated before. We measured STC-1 in cerebrospinal fluid (CSF) samples from a total of 163 individuals including AD, prodromal AD (pAD), mixed AD, stable mild cognitive impairment (sMCI), and diagnoses of other dementia than AD, as well as cognitively normal controls (CNC) enrolled at academic centers in France and Sweden. STC-1 concentration was reliably measureable in all CSF samples and was significantly increased in the initial exploratory cohort of neurochemically enriched AD patients versus AD biomarker-negative controls. In the second cohort, STC-1 was increased in AD versus pAD, and other dementia disorders, but the difference was not statistically significant. In the third cohort, there was no significant difference in STC-1 concentration between AD and CNC; however, STC-1 concentration was significantly decreased in patients with other dementia disorders compared with AD and CNC. Taken together, CSF STC-1 showed an increasing trend in AD, but the findings were not consistent across the three study cohorts. In contrast, CSF STC-1 concentrations were reduced in patients with dementia diagnoses other than AD, as compared with both AD patients and CNC. The findings from these studies suggest CSF STC-1 as a potential biomarker in differential diagnosis of dementias.

A proteomic atlas of senescence-associated secretomes for aging biomarker development

“…Strikingly, one cluster, consisting of just three proteins-chemokine C-X-C motif ligand 1 (CXCL1), MMP1, and stanniocalcin 1 (STC1)-were highly represented in the sSASPs of all inducers, suggesting these proteins might serve as surrogate markers of the sSASP. Of note, STC1, among the top sSASP proteins, is a previously unidentified SASP factor and a secreted hormone with many disease associations [35][36][37][38][39][40]. Our analyses also validate MMP1 and CXCL1 as SASP markers.…”

“…Additionally, two of the top core sSASP proteins identified by an unbiased k-means clustering algorithm-STC1 and MMP1 (Fig 7B and 7C)-were reported as significant aging biomarkers [48]. In addition to aging, MMP1 has been identified as a biomarker for several cancers, pulmonary fibrosis, and potentially Alzheimer's disease [68][69][70][71], whereas STC1 has been identified as a diagnostic and prognostic biomarker for cancers, pulmonary fibrosis, renal ischemia/reperfusion injury, and Alzheimer's disease [35][36][37][38][39][40].…”

Correlation Between Plasma CircRNA-089763 and Postoperative Cognitive Dysfunction in Elderly Patients Undergoing Non-cardiac Surgery

“…CircRNA-089763 also adsorbs miR-6798-3p and miR-3684, which may commonly regulate target genes of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma genes (YWHAG) and stanniocalcin 1 (STC-1). Research found that STC-1 in the CSF can be used as a biomarker for the differential diagnosis of dementia ( Shahim et al, 2017 ). Ramocki et al (2010) found that changes in cognitive function and behavioral ability were associated with abnormal expression of the YWHAG gene.…”

A Proteomic Atlas of Senescence-Associated Secretomes for Aging Biomarker Development

“…Alzheimer's disease Du et al, 2016;Ohkouchi et al, 2015;Pan et al, 2015;Shahim et al, 2017;Su et al, 2015). The enrichment of aging and disease biomarkers in the secretomes of senescent cells supports their links to a wide spectrum of age-related diseases and highlights the need for comprehensive secretome profiles of senescent cells in multiple biological contexts.…”

“…Strikingly, one cluster consisting of just three proteins -chemokine (C-X-C motif) ligand 1 (CXCL1), matrix metallopeptidase 1 (MMP1), and stanniocalcin 1 (STC1) -were very highly present in the sSASP of all inducers, suggesting that these proteins are best qualified to serve as surrogate markers of the sSASP. Of note, among the top expressed sSASP proteins was STC1, a previously unidentified SASP factor and a secreted hormone with many disease associations Du et al, 2016;Ohkouchi et al, 2015;Pan et al, 2015;Shahim et al, 2017;Su et al, 2015), demonstrating the utility of robust unbiased approaches to uncovering novel molecules, biological functions and pathways. Our approach also validates MMP1 and CXCL1 as SASP markers.…”