{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T12:08:16Z","timestamp":1789560496213,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T00:00:00Z","timestamp":1735344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T00:00:00Z","timestamp":1735344000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["FWO\/G093218N"],"award-info":[{"award-number":["FWO\/G093218N"]}],"id":[{"id":"10.13039\/501100003130","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":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>The longitudinal progression of synaptic loss in Alzheimer's disease (AD) and how it is affected by tau pathology remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Thirty patients with amnestic mild cognitive impairment (aMCI) and 26 healthy controls underwent cognitive evaluations and tau, synaptic vesicle protein 2A (SV2A), and amyloid positron emission tomography. Twenty\u2010one aMCI underwent 2\u2010year follow\u2010up (FU) investigations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Tau levels in aMCI increased longitudinally in Braak regions III through VI but not in Braak regions I and II. SV2A decreased longitudinally in all Braak regions in aMCI. Baseline tau was negatively associated with longitudinal SV2A loss in early Braak regions and with SV2A at FU across regions. Baseline tau and longitudinal change in SV2A were associated with longitudinal cognitive decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Tau accumulation reaches a plateau in early Braak regions already in the aMCI stage of AD. In early Braak regions, the association between baseline tau and longitudinal SV2A loss might reflect synaptic dysfunction caused by tau pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Tau accumulation reached a plateau in early Braak regions in amnestic mild cognitive impairment (aMCI) patients.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>aMCI patients show widespread longitudinal decrease in synaptic vesicle protein 2A (SV2A) over 2 years.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Baseline tau was predictive for longitudinal SV2A loss.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The tau\u2013SV2A relation showed individual variability and was negative across patients.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Baseline tau and longitudinal SV2A change were associated with change in cognition.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14412","type":"journal-article","created":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T21:08:36Z","timestamp":1735420116000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Longitudinal synaptic loss versus tau Braak staging in amnestic mild cognitive 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