{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T13:48:35Z","timestamp":1781531315573,"version":"3.54.5"},"reference-count":76,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T00:00:00Z","timestamp":1667174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bando Ricerca Salute 2018","award":["DSB. AD006.289"],"award-info":[{"award-number":["DSB. AD006.289"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the leading cause of dementia, but the pathogenetic factors are not yet well known, and the relationships between brain and systemic biochemical derangements and disease onset and progression are unclear. We aim to focus on blood biomarkers for an accurate prognosis of the disease. We used a dataset characterized by longitudinal findings collected over the past 10 years from 90 AD patients. The dataset included 277 observations (both clinical and biochemical ones, encompassing blood analytes encompassing routine profiles for different organs, together with immunoinflammatory and oxidative markers). Subjects were grouped into four severity classes according to the Clinical Dementia Rating (CDR) Scale: mild (CDR = 0.5 and CDR = 1), moderate (CDR = 2), severe (CDR = 3) and very severe (CDR = 4 and CDR = 5). Statistical models were used for the identification of potential blood markers of AD progression. Moreover, we employed the Pathfinder tool of the Reactome database to investigate the biological pathways in which the analytes of interest could be involved. Statistical results reveal an inverse significant relation between four analytes (high-density cholesterol, total cholesterol, iron and ferritin) with AD severity. In addition, the Reactome database suggests that such analytes could be involved in pathways that are altered in AD progression. Indeed, the identified blood markers include molecules that reflect the heterogeneous pathogenetic mechanisms of AD. The combination of such blood analytes might be an early indicator of AD progression and constitute useful therapeutic targets.<\/jats:p>","DOI":"10.3390\/ijms232113289","type":"journal-article","created":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T06:01:28Z","timestamp":1667282488000},"page":"13289","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Blood Analytes as Biomarkers of Mechanisms Involved in Alzheimer\u2019s Disease Progression"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2003-7604","authenticated-orcid":false,"given":"Andrea","family":"Baldini","sequence":"first","affiliation":[{"name":"Department of Information Engineering, Faculty of Engineering, University of Pisa, 56122 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4822-5562","authenticated-orcid":false,"given":"Alberto","family":"Greco","sequence":"additional","affiliation":[{"name":"Department of Information Engineering, Faculty of Engineering, University of Pisa, 56122 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirko","family":"Lomi","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Giannelli","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Canale","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7247-6994","authenticated-orcid":false,"given":"Andrea","family":"Diana","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Dolciotti","sequence":"additional","affiliation":[{"name":"Medical Specialties Department, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy"},{"name":"NeuroCare onlus, 56121 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Del Carratore","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Bongioanni","sequence":"additional","affiliation":[{"name":"Medical Specialties Department, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy"},{"name":"NeuroCare onlus, 56121 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S1474-4422(16)00070-3","article-title":"CSF and blood biomarkers for the diagnosis of Alzheimer\u2019s disease: A systematic review and meta-analysis","volume":"15","author":"Olsson","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/bs.pmbts.2019.06.003","article-title":"Blood-brain barrier and innate immunity in the pathogenesis of Alzheimer\u2019s disease","volume":"168","author":"Horvat","year":"2019","journal-title":"Prog. 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