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To individuate peptides and\/or proteins with diagnostic potential for early diagnosis, severity and discrimination from similar pathologies, the salivary proteome in 36 PD patients was investigated in comparison with 36 healthy controls (HC) and 35 Alzheimer's disease (AD) patients. A top\u2010down platform based on HPLC\u2010ESI\u2010IT\u2010MS allowed characterizing and quantifying intact peptides, small proteins and their PTMs (overall 51). The three groups showed significantly different protein profiles, PD showed the highest levels of cystatin SA and antileukoproteinase and the lowest of cystatin SN and some statherin proteoforms. HC exhibited the lowest abundance of thymosin \u03b24, short S100A9, cystatin A, and dimeric cystatin B. AD patients showed the highest abundance of \u03b1\u2010defensins and short oxidized S100A9. Moreover, different proteoforms of the same protein, as S\u2010cysteinylated and S\u2010glutathionylated cystatin B, showed opposite trends in the two pathological groups. Statherin, cystatins SA and SN classified accurately PD from HC and AD subjects. \u03b1\u2010defensins, histatin 1, oxidized S100A9, and P\u2010B fragments were the best classifying factors between PD and AD patients. Interestingly statherin and thymosin \u03b24 correlated with defective olfactory functions in PD patients. All these outcomes highlighted implications of specific proteoforms involved in the innate\u2010immune response and inflammation regulation at oral and systemic level, suggesting a possible panel of molecular and clinical markers suitable to recognize subjects affected by PD.<\/jats:p>","DOI":"10.1002\/pmic.202300202","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T18:49:18Z","timestamp":1691174958000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["A top\u2010down proteomic approach reveals a salivary protein profile able to classify Parkinson's disease with respect to Alzheimer's disease patients and to healthy controls"],"prefix":"10.1002","volume":"24","author":[{"given":"Cristina","family":"Contini","sequence":"first","affiliation":[{"name":"Department of Life and Environmental Sciences University of Cagliari Cittadella Universitaria Monserrato  Monserrato CA Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Fadda","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health Institute of Neurology  Cagliari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greca","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences University of Cagliari Cittadella Universitaria Monserrato  Monserrato CA Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Masala","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Cagliari Cittadella Univ. 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