{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T05:17:07Z","timestamp":1755839827176,"version":"3.40.5"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T00:00:00Z","timestamp":1743292800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T00:00:00Z","timestamp":1743292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL126056","R01HL126056","R01HL126056"],"award-info":[{"award-number":["R01HL126056","R01HL126056","R01HL126056"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R03AG063328","R03AG063328","R03AG063328","R03AG063328"],"award-info":[{"award-number":["R03AG063328","R03AG063328","R03AG063328","R03AG063328"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biogerontology"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Nicotinic acetylcholine receptors (nAChRs) are important regulators of brain and immune function that play critical roles in the neuropathology and progression of Alzheimer\u2019s disease and related dementias (ADRD). However, quantifying nAChRs in the brain remains elusive, and little is known about peripheral measures of nAChR in older adults or their relationship to cognition. Here, we examined associations between nAChR expression and immunoregulatory function in peripheral blood monocytes and cognitive performance among 167 older adults (age 72.3\u2009\u00b1\u20097.6\u00a0years; 71% female). Penalized linear and logistic regression were used to identify nAChR-related features in classical, intermediate, and nonclassical monocytes, as well as immunophenotypes, clinical and sociodemographic factors, associated with cognitive status (Montreal Cognitive Assessment; MoCA). Intermediate monocytes had the highest expression of alpha-7 nAChRs and greater ex vivo inflammatory responses (83.7% TNF-\u0251<jats:sup>+<\/jats:sup> cells) relative to classical (68.4%, <jats:italic>d<\/jats:italic>\u2009=\u20091.98, <jats:italic>P\u2009<\/jats:italic>&lt;\u20090.001) or nonclassical monocytes (58.9%, <jats:italic>d<\/jats:italic>\u2009=\u20093.20, <jats:italic>P\u2009<\/jats:italic>&lt;\u20090.001). Participants with mild cognitive impairment (MCI: <jats:italic>N<\/jats:italic>\u2009=\u200976) had higher soluble CD14 levels (1777\u2009\u00b1\u2009377\u00a0pg\/uL) and greater anticholinergic medication burden (ACB; mean\u2009=\u20091.76) than normocognitive participants (NC: <jats:italic>N<\/jats:italic>\u2009=\u200991; 1638\u2009\u00b1\u2009352\u00a0pg\/uL sCD14, <jats:italic>t<\/jats:italic>\n            <jats:sub>155<\/jats:sub>\u2009=\u20092.78, <jats:italic>P\u2009<\/jats:italic>=\u20090.006; mean ACB: 1.05, <jats:italic>t<\/jats:italic>\n            <jats:sub>143<\/jats:sub>\u2009=\u20093.13, <jats:italic>P\u2009<\/jats:italic>=\u20090.002). Multivariate regression models indicated that stronger nAChR-mediated immunoregulation in intermediate monocytes was associated with higher MoCA scores (beta\u2009=\u20090.13) and 14% lower odds of MCI, as well as lower ACB (beta\u2009=\u2009\u2212 2.10; 95% CI \u2212 4.14, \u2212 0.61). This study demonstrates that peripheral monocytes exhibit subset-specific differences in nAChR phenotypes in older adults and provides preliminary evidence for their association with cognitive function and a potential mediating role between ACB and cognitive impairment.<\/jats:p>","DOI":"10.1007\/s10522-025-10220-3","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T08:11:33Z","timestamp":1743495093000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Elucidating the role of peripheral monocyte nicotinic acetylcholine receptors and inflammation in cognitive outcomes in older adults"],"prefix":"10.1007","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8546-2076","authenticated-orcid":false,"given":"Jordan N.","family":"Kohn","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavrila","family":"Ang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Pruitt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Gandarilla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Tu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzi","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,3,30]]},"reference":[{"key":"10220_CR1","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1038\/s41582-021-00549-x","volume":"17","author":"BM Bettcher","year":"2021","unstructured":"Bettcher BM, Tansey MG, Doroth\u00e9e G, Heneka MT (2021) Peripheral and central immune system crosstalk in Alzheimer disease\u2014a research prospectus. Nat Rev Neurol 17:689\u2013701. https:\/\/doi.org\/10.1038\/s41582-021-00549-x","journal-title":"Nat Rev Neurol"},{"key":"10220_CR2","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1002\/ddr.22085","volume":"84","author":"LH Burns","year":"2023","unstructured":"Burns LH, Pei Z, Wang H (2023) Targeting \u03b17 nicotinic acetylcholine receptors and their protein interactions in Alzheimer\u2019s disease drug development. Drug Dev Res 84:1085\u20131095. https:\/\/doi.org\/10.1002\/ddr.22085","journal-title":"Drug Dev Res"},{"key":"10220_CR3","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s12979-022-00321-9","volume":"19","author":"Y Cao","year":"2022","unstructured":"Cao Y, Fan Y, Li F et al (2022) Phenotypic and functional alterations of monocyte subsets with aging. 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JCI Insight. https:\/\/doi.org\/10.1172\/jci.insight.146215","journal-title":"JCI Insight"}],"container-title":["Biogerontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10522-025-10220-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10522-025-10220-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10522-025-10220-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T16:38:04Z","timestamp":1746635884000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10522-025-10220-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,30]]},"references-count":26,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10220"],"URL":"https:\/\/doi.org\/10.1007\/s10522-025-10220-3","relation":{},"ISSN":["1389-5729","1573-6768"],"issn-type":[{"type":"print","value":"1389-5729"},{"type":"electronic","value":"1573-6768"}],"subject":[],"published":{"date-parts":[[2025,3,30]]},"assertion":[{"value":"23 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures performed involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"82"}}