{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:46:14Z","timestamp":1768567574795,"version":"3.49.0"},"posted":{"date-parts":[[2025,5,6]]},"group-title":"Occupational and Environmental Health","reference-count":134,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Interest is growing in the potential role of manganese (Mn) in Alzheimer\u2019s Disease (ADRD). This nested pilot study of a ferroalloy workers cohort was aimed to investigate the effects of long-term occupational Mn exposure on cognitive function through \u03b2-amyloid (A\u03b2) modification and brain deposition, as well as metabolomic, lipidomic and proteomic profiling. We examined 6 male exposed workers (median age 63, exposure duration 31 yrs), and 5 historical controls (median age 60) who had undergone brain PET scan imaging showing higher A\u03b2 deposition among the exposed compared to the controls (p &lt; 0.05). The average annual cumulative respirable Mn of the ferroalloy workers was 329.23 \u00b1 516.39 \u00b5g\/m\n                  <jats:sup>3<\/jats:sup>\n                  (geometric mean 118.59). Average Mn level in plasma of the exposed subjects (0.704 \u00b1 0.2 ng\/mL) was significantly higher than the controls (0.397 \u00b1 0.18). Pathway analyses using LC-MS\/MS results revealed impacted metabolomic pathways such as olfactory signaling, mitochondrial fatty acid beta-oxidation, biogenic amine synthesis, SLC-mediated transmembrane transport, and glycerophospholipid and choline metabolism in the Mn exposed group. Single molecule arrays (Simoa) analysis revealed notable modifications of AD-related plasma biomarkers; protein microarray (chip) showed significant changes (p &lt; 0.05) in the levels of some plasma antibodies targeting autoimmune and neuronal associated proteins such as A\u03b2 (25-35), GFAP, Serotonin, Human NOVA1, and Human Siglec-1\/CD169 among the Mn exposed individuals. This data provides evidence on Mn-induced alterations of pathways and biomarkers associated with cognitive neurodegenerative diseases.\n                <\/jats:p>","DOI":"10.1101\/2025.05.02.25326824","type":"posted-content","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:45:34Z","timestamp":1746578734000},"source":"Crossref","is-referenced-by-count":0,"title":["Impact of Manganese on Neuronal Function: An Exploratory MultiOmic Study on Ferroalloy Workers in Brescia, Italy"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4951-614X","authenticated-orcid":false,"given":"Somaiyeh","family":"Azmoun","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5606-8926","authenticated-orcid":false,"given":"Freeman","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Shoieb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Colicino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isha","family":"Winters","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiwei","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7832-8423","authenticated-orcid":false,"given":"Hari","family":"Krishnamurthy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donatella","family":"Placidi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Lambertini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto G","family":"Lucchini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025050806050636000_2025.05.02.25326824v1.1","doi-asserted-by":"crossref","unstructured":"Martins, A.C., Jr. , et al., New Insights on the Role of Manganese in Alzheimer\u2019s Disease and Parkinson\u2019s Disease. 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