{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T16:26:21Z","timestamp":1761582381829,"version":"build-2065373602"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T00:00:00Z","timestamp":1728518400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K07474"],"award-info":[{"award-number":["22K07474"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["18he1402003h0003"],"award-info":[{"award-number":["18he1402003h0003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;D Transl Res &amp; Clin Interv"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Previous studies have examined the predictive accuracy of plasma amyloid beta (A\u03b2) biomarkers in clinical cohorts. However, their accuracy for predicting amyloid\u2010positive patients in community\u2010based cohorts is unclear. This study aimed to determine the predictive accuracy of A\u03b2 precursor protein 669\u2010711\/A\u03b21\u201042, A\u03b21\u201040\/1\u201042 and their composite biomarkers for brain amyloid deposition or the clinical progression in community\u2010dwelling older adults with mild cognitive impairment (MCI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>This prospective cohort study was conducted from August 2015 to September 2019. Subsequently, the participants underwent follow\u2010up cognitive assessments up to 8 years after the start of the study. Blood samples were collected from older adults aged \u2265 65 years with MCI at baseline. Plasma A\u03b2 biomarkers were analyzed using immunoprecipitation\u2010mass spectrometry. The accuracy of plasma biomarkers for brain amyloid status was evaluated using receiver operating characteristic curve analysis. Relationships between comorbidities and plasma A\u03b2 markers were examined using multiple linear regression analysis. Associations of plasma biomarkers with clinical conversion to Alzheimer's disease (AD) dementia were evaluated using Kaplan\u2012Meier curves.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      The participants included 107 patients (57 [53.3%] females, median age: 76.0 [72.0\u201380.0] years). Plasma biomarkers correlated with cortical amyloid uptake (\n                      <jats:italic>\u03c1<\/jats:italic>\n                      = 0.667\u20130.754). The composite biomarker had the best area under the curve (0.943, 95% confidence interval [CI]: 0.901 to 0.985) for predicting amyloid positivity. Apolipoprotein \u03b54 status showed significant correlations with increased plasma amyloid biomarker levels. Participants with high composite biomarker levels at baseline had a greater risk of conversion to AD dementia (hazard ratio 10.74, 95% CI: 3.51 to 32.84,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001). The higher composite biomarker was associated with a faster rate of cognitive decline (\n                      <jats:italic>\u03c1<\/jats:italic>\n                      = \u22120.575,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Plasma A\u03b2 composite biomarker may serve as a surrogate measure for amyloid deposition and a predictor of disease progression in a community\u2010based cohort.<\/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>Plasma amyloid beta (A\u03b2) biomarkers correlated with 11C\u2010Pittsburgh compound B uptake, mainly in the frontal\/parietotemporal cortices and posterior cingulate gyrus.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The amyloid composite biomarker can predict amyloid positron emission tomography positivity with a high area under the curve of 0.943 in a community\u2010based mild cognitive impairment cohort.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The higher amyloid composite biomarker at baseline was significantly associated with worsening Mini\u2010Mental State Examination score and a high risk for developing Alzheimer's disease (AD) dementia over 8 years.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The amyloid composite biomarker can predict clinical progression to AD dementia with a high area under the curve of 0.860.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Apolipoprotein E \u03b54 status influenced the plasma A\u03b2 biomarker levels.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.70008","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T08:38:30Z","timestamp":1728549510000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Plasma amyloid beta biomarkers predict amyloid positivity and longitudinal clinical progression in mild cognitive impairment"],"prefix":"10.1002","volume":"10","author":[{"given":"Takuya","family":"Ataka","sequence":"first","affiliation":[{"name":"Department of Neurology Faculty of Medicine Oita University  Oita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7137-7268","authenticated-orcid":false,"given":"Noriyuki","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Neurology Faculty of Medicine Oita University  Oita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Koichi Tanaka Mass Spectrometry Research Laboratory Shimadzu Corporation  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teruaki","family":"Masuda","sequence":"additional","affiliation":[{"name":"Department of Neurology Faculty of Medicine Oita University  Oita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosuke","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Department of Neurology Faculty of Medicine Oita University  Oita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenichi","family":"Yabuuchi","sequence":"additional","affiliation":[{"name":"Department of Neurology Faculty of Medicine Oita University  Oita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Mizukami","sequence":"additional","affiliation":[{"name":"Department of Neurology Faculty of Medicine Oita University  Oita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsukasa","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Koichi Tanaka Mass Spectrometry Research Laboratory Shimadzu Corporation  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Temmei","family":"Ito","sequence":"additional","affiliation":[{"name":"Eisai Co. 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