{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:08:04Z","timestamp":1791223684320,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["RCYX20221008092935096"],"award-info":[{"award-number":["RCYX20221008092935096"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82422027"],"award-info":[{"award-number":["82422027"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U24A20340"],"award-info":[{"award-number":["U24A20340"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171197"],"award-info":[{"award-number":["82171197"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Baseline and longitudinal characteristics of cerebrospinal fluid (CSF) growth\u2010associated protein 43 (GAP\u201043) and plasma neurofilament light (NfL) and how they correlate interactively with neurodegeneration and cognitive decline in Alzheimer's disease (AD) are not fully understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We investigated dynamic changes of CSF GAP\u201043 and plasma NfL across different AD stages and their association with longitudinal neurodegeneration and cognitive decline up to 12 years.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Individuals with hippocampal atrophy, AD\u2010signature cortical thinning, or hypometabolism (N+) had faster plasma NfL increase rates than healthy individuals, regardless of amyloid\/tau status. In contrast, none of these N+ imaging indicators correlated with more rapid increases in CSF GAP\u201043. Furthermore, CSF GAP\u201043 and plasma NfL synergistically predicted subsequent gray matter atrophy, cortical thinning, hypometabolism of the middle temporal region, and cognition.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>CSF GAP\u201043\u2010associated presynaptic loss indicates tau\u2010dependent early neurodegeneration, whereas the axonal degeneration indicated by plasma NfL is a relatively late atrophy\/hypometabolism\u2010associated fluid neurodegeneration biomarker.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Plasma neurofilament light (NfL) was increased in N+ or cognitively impaired individuals.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Increases in tau\u2010dependent cerebrospinal fluid CSF growth\u2010associated protein 43 (GAP\u201043) before imaging neurodegeneration indicators.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>CSF GAP\u201043 and plasma NfL are synergistically related to longitudinal neurodegeneration.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>CSF GAP\u201043 and plasma NfL are synergistically related to longitudinal cognitive decline.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.70080","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T11:11:14Z","timestamp":1749726674000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Presynaptic loss and axonal degeneration synergistically correlate with longitudinal neurodegeneration and cognitive decline"],"prefix":"10.1002","volume":"21","author":[{"given":"Dai","family":"Shi","sequence":"first","affiliation":[{"name":"Neurology Medicine Center The Seventh Affiliated Hospital Sun Yat\u2010sen University  Shenzhen 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