Salivary Proteomics Identifies Transthyretin as a Biomarker of Early Dementia Conversion.
| Autor: | Eldem E; Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland.; Swiss Integrative Center for Human Health, Fribourg, Switzerland., Barve A; Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland.; Swiss Integrative Center for Human Health, Fribourg, Switzerland., Sallin O; Swiss Integrative Center for Human Health, Fribourg, Switzerland., Foucras S; Hôpital Cantonal Fribourgeois, Fribourg, Switzerland., Annoni JM; Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland.; Hôpital Cantonal Fribourgeois, Fribourg, Switzerland., Schmid AW; Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., Alberi Auber L; Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland.; Swiss Integrative Center for Human Health, Fribourg, Switzerland. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of Alzheimer's disease reports [J Alzheimers Dis Rep] 2022 Feb 02; Vol. 6 (1), pp. 31-41. Date of Electronic Publication: 2022 Feb 02 (Print Publication: 2022). |
| DOI: | 10.3233/ADR-210056 |
| Abstrakt: | Background: Alzheimer's disease (AD) remains to date an incurable disease with a long asymptomatic phase. Early diagnosis in peripheral biofluids has emerged as key for identifying subjects at risk and developing therapeutics and preventative approaches. Objective: We apply proteomics discovery to identify salivary diagnostic biomarkers for AD, which are suitable for self-sampling and longitudinal biomonitoring during aging. Methods: 57 participants were recruited for the study and were categorized into Cognitively normal (CNh) ( n = 19), mild cognitive impaired (MCI) ( n = 21), and Alzheimer's disease (AD) ( n = 17). On a subset of subjects, 3 CNh and 3 mild AD, shot-gun filter aided sample preparation (FASP) proteomics and liquid chromatography mass spectroscopy (LC-MS/MS) was employed in saliva and cerebrospinal fluid (CSF) to identify neural-derived proteins. The protein level of salivary Transthyretin (TTR) was validated using western blot analysis across groups. Results: We found that 19.8% of the proteins in saliva are shared with CSF. When we compared the saliva and CSF proteome, 24 hits were decreased with only one protein expressed more. Among the differentially expressed proteins, TTR with reported function in amyloid misfolding, shows a significant drop in AD samples, confirmed by western blot showing a 0.5-fold reduction in MCI and AD compared to CNh. Conclusion: A reduction in salivary TTR appears with the onset of cognitive symptoms. More in general, the proteomic profiling of saliva shows a plethora of biomarkers worth pursuing as non-invasive hallmarks of dementia in the preclinical stage. Competing Interests: The authors have no conflict of interest to report. (© 2022 – The authors. Published by IOS Press.) |
| Databáze: | MEDLINE |
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