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However, NAbs pathological relevance in\u00a0Alzheimer\u2019s disease (AD) is not well-understood.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Twenty-eight candidate proteins encoded by AD-associated genes were selected for this study based on a number of selection criteria, including preferential expression in the brain and B-lymphocyte cells. The levels of NAbs in plasma were analyzed according to their epitopes in age- and gender-matched cognitively normal subjects (CN, <jats:italic>n<\/jats:italic>\u2009=\u200956), subjects with mild cognitive impairment (MCI, <jats:italic>n<\/jats:italic>\u2009=\u200916) and subjects with AD (<jats:italic>n<\/jats:italic>\u2009=\u200956). We aimed to study the levels of their NAbs in plasma and their associations with cognitive decline in individuals with AD.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Of the 28 antigens tested, 17 showed decreased NAbs in individuals with AD; in particular, NAb-TREM2 had an area under the ROC curve of 0.806, with the highest sensitivity (0.370) at 95% specificity among all 28 tests. Further protein\u2013protein interaction networks and functional enrichment analysis suggested that target genes were\u00a0enriched in AD-related pathological processes classified under \u201cAlzheimer\u2019s disease\u201d, \u201cneurodegenerative disease\u201d and \u201camyloidosis\u201d. The \u201cAlzheimer\u2019s disease\u201d and \u201cneurodegenerative disease\u201d clusters, which converged on the initial \u201crecognition\u201d step of microglial phagocytosis, showed the best diagnostic performance for AD.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This study suggests a decline in the function of the adaptive immune system in AD, and the levels of circulating NAbs are likely to serve as biomarkers for surveilling the progression of AD.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12974-023-02750-9","type":"journal-article","created":{"date-parts":[[2023,3,26]],"date-time":"2023-03-26T20:38:39Z","timestamp":1679863119000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Decrease in naturally occurring antibodies against epitopes of Alzheimer\u2019s disease (AD) risk gene products is associated with cognitive decline in AD"],"prefix":"10.1186","volume":"20","author":[{"given":"Dongmei","family":"Gu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luchun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huali","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"2750_CR1","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/s41583-021-00533-w","volume":"23","author":"GB Frisoni","year":"2022","unstructured":"Frisoni GB, Altomare D, Thal DR, Ribaldi F, van der Kant R, Ossenkoppele R, Blennow K, Cummings J, van Duijn C, Nilsson PM, et al. 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Written informed consent was obtained from all participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors agree with publication of the current manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"All authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"74"}}