{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T09:27:06Z","timestamp":1788514026457,"version":"build-2803163510"},"reference-count":48,"publisher":"SAGE Publications","issue":"s1","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2024,8,20]]},"abstract":"<jats:p>Background: Synaptic dysfunction is closely associated with cognitive function in Alzheimer\u2019s disease (AD), and is present already in an early stage of the disease. Objective: Using serial cerebrospinal fluid (CSF) sampling, we aimed to investigate slopes of CSF synaptic proteins, and their relation with cognition along the AD continuum. Methods: We included subjects with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) (n\u200a=\u200a50 amyloid-\u03b2+ [A\u200a+], n\u200a=\u200a50 A\u2013) and 50 patients with AD dementia from the Amsterdam dementia cohort, with CSF at two time points (median[IQR] 2.1[1.4\u20132.7] years). We analyzed 17 synaptic proteins and neurofilament light (NfL). Using linear mixed models we assessed trajectories of protein levels, and associations with cognitive decline (repeated Mini-Mental State Examination). We used Cox regression models to assess predictive value of protein levels for progression to AD dementia. Results: At baseline most proteins showed increased levels in AD dementia compared to the other groups. In contrast NPTX2 levels were lower in AD dementia. Higher baseline levels of SNAP25, \u03b2-syn, and 14-3-3 proteins were associated with faster cognitive decline (St.B[SE] \u20130.27[0.12] to \u20130.61[0.12]). Longitudinal analyses showed that SYT1 and NPTX levels decreased over time in AD dementia (st.B[SE] \u20130.10[0.04] to \u20130.15[0.05]) and SCD\/MCI-A+ (St.B[SE] \u20130.07[0.03] to \u20130.12[0.03]), but not in SCD\/MCI-A- (pinteraction\u200a&lt;\u200a0.05). Increase over time in NfL levels was associated with faster cognitive decline in AD dementia (St.B[SE] \u20131.75[0.58]), but not in the other groups (pinteraction\u200a&lt;\u200a0.05). Conclusions: CSF synaptic proteins showed different slopes over time, suggesting complex synaptic dynamics. High levels of especially SNAP-25 may have value for prediction of cognitive decline in early AD stages, while increase in NfL over time correlates better with cognitive decline in later stages.<\/jats:p>","DOI":"10.3233\/jad-240610","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T12:31:21Z","timestamp":1723206681000},"page":"S103-S114","source":"Crossref","is-referenced-by-count":11,"title":["Serial Cerebrospinal Fluid Sampling Reveals Trajectories of Potential Synaptic Biomarkers in Early Stages of Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"100","author":[{"given":"Flora H.","family":"Duits","sequence":"first","affiliation":[{"name":"Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands"},{"name":"Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands"},{"name":"Department of Laboratory Medicine, Neurochemistry Lab, Amsterdam Neuroscience, Amsterdam UMC, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, M\u00f6lndal, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, M\u00f6lndal, Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, M\u00f6lndal, Sweden"},{"name":"Department of Neurodegenerative Disease and UK Dementia Research Institute, UCL Institute of Neurology, London, UK"},{"name":"Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China"},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, M\u00f6lndal, Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, M\u00f6lndal, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiesje M.","family":"van der Flier","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands"},{"name":"Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands"},{"name":"Department of Epidemiology and Biostatistics, Amsterdam UMC, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte E.","family":"Teunissen","sequence":"additional","affiliation":[{"name":"Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands"},{"name":"Department of Laboratory Medicine, Neurochemistry Lab, Amsterdam Neuroscience, Amsterdam UMC, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Brinkmalm","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, M\u00f6lndal, Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, M\u00f6lndal, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-240610_ref1","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S1474-4422(16)00070-3","article-title":"CSF and 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