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Associations were investigated between CSF GAP-43 and clinical diagnosis, A\u03b2\/tau\/neurodegeneration (AT(N)) status, CSF and blood biomarkers of AD, cognitive measurements and brain neuroimaging findings. CSF GAP-43 levels were increased in patients with AD dementia (mean, 6331.05\u00a0pg\/ml) compared with the CN (mean, 5001.05\u00a0pg\/ml) and MCI (mean, 5118.8\u00a0pg\/ml) (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) groups. CSF GAP-43 correlated with CSF phosphorylated tau 181(p-tau) (r\u2009=\u20090.768, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001), and had high diagnostic accuracy in differentiating tau positive status vs. tau negative status (area under the receiver operating characteristic curve, 0.8606). CSF GAP-43 was particularly elevated among individuals with tau positive status. High CSF GAP-43 was associated with longitudinal deterioration of cognitive scores and brain neuroimaging findings. CSF GAP-43 was associated with a clinical diagnosis of AD dementia and with an individual\u2019s tau status, cognitive measurements and findings from neuroimaging. This study implies that CSF GAP-43 as a biomarker of synaptic dysfunction could predict the disease progression of AD patients.<\/jats:p>","DOI":"10.1038\/s41598-022-20324-2","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T15:04:54Z","timestamp":1666019094000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["CSF GAP-43 as a biomarker of synaptic dysfunction is associated with tau pathology in Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"12","author":[{"given":"Qiang","family":"Qiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loren","family":"Skudder-Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Toyota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenshi","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Adachi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,17]]},"reference":[{"key":"20324_CR1","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/j.bcp.2014.01.015","volume":"88","author":"CR Overk","year":"2014","unstructured":"Overk, C. 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