{"title":"血浆淀粉样β生物标志物可预测轻度认知障碍患者的淀粉样蛋白阳性率和纵向临床进展","authors":"Takuya Ataka, Noriyuki Kimura, Naoki Kaneko, Teruaki Masuda, Yosuke Takeuchi, Kenichi Yabuuchi, Takeshi Mizukami, Tsukasa Takeuchi, Temmei Ito, Hideaki Tasai, Takehiko Miyagawa, Shunya Hanai, Shinichi Iwamoto, Etsuro Matsubara","doi":"10.1002/trc2.70008","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> INTRODUCTION</h3>\n \n <p>Previous studies have examined the predictive accuracy of plasma amyloid beta (Aβ) biomarkers in clinical cohorts. However, their accuracy for predicting amyloid-positive patients in community-based cohorts is unclear. This study aimed to determine the predictive accuracy of Aβ precursor protein 669-711/Aβ1-42, Aβ1-40/1-42 and their composite biomarkers for brain amyloid deposition or the clinical progression in community-dwelling older adults with mild cognitive impairment (MCI).</p>\n </section>\n \n <section>\n \n <h3> METHODS</h3>\n \n <p>This prospective cohort study was conducted from August 2015 to September 2019. Subsequently, the participants underwent follow-up cognitive assessments up to 8 years after the start of the study. Blood samples were collected from older adults aged ≥ 65 years with MCI at baseline. Plasma Aβ biomarkers were analyzed using immunoprecipitation-mass spectrometry. The accuracy of plasma biomarkers for brain amyloid status was evaluated using receiver operating characteristic curve analysis. Relationships between comorbidities and plasma Aβ 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‒Meier curves.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>The participants included 107 patients (57 [53.3%] females, median age: 76.0 [72.0–80.0] years). Plasma biomarkers correlated with cortical amyloid uptake (<i>ρ</i> = 0.667–0.754). 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 ε4 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, <i>P</i> < 0.001). The higher composite biomarker was associated with a faster rate of cognitive decline (<i>ρ</i> = −0.575, <i>P</i> < 0.001).</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>Plasma Aβ composite biomarker may serve as a surrogate measure for amyloid deposition and a predictor of disease progression in a community-based cohort.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>Plasma amyloid beta (Aβ) biomarkers correlated with 11C-Pittsburgh compound B uptake, mainly in the frontal/parietotemporal cortices and posterior cingulate gyrus.</li>\n \n <li>The amyloid composite biomarker can predict amyloid positron emission tomography positivity with a high area under the curve of 0.943 in a community-based mild cognitive impairment cohort.</li>\n \n <li>The higher amyloid composite biomarker at baseline was significantly associated with worsening Mini-Mental State Examination score and a high risk for developing Alzheimer's disease (AD) dementia over 8 years.</li>\n \n <li>The amyloid composite biomarker can predict clinical progression to AD dementia with a high area under the curve of 0.860.</li>\n \n <li>Apolipoprotein E ε4 status influenced the plasma Aβ biomarker levels.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":null,"pages":null},"PeriodicalIF":4.9000,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70008","citationCount":"0","resultStr":"{\"title\":\"Plasma amyloid beta biomarkers predict amyloid positivity and longitudinal clinical progression in mild cognitive impairment\",\"authors\":\"Takuya Ataka, Noriyuki Kimura, Naoki Kaneko, Teruaki Masuda, Yosuke Takeuchi, Kenichi Yabuuchi, Takeshi Mizukami, Tsukasa Takeuchi, Temmei Ito, Hideaki Tasai, Takehiko Miyagawa, Shunya Hanai, Shinichi Iwamoto, Etsuro Matsubara\",\"doi\":\"10.1002/trc2.70008\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> INTRODUCTION</h3>\\n \\n <p>Previous studies have examined the predictive accuracy of plasma amyloid beta (Aβ) biomarkers in clinical cohorts. However, their accuracy for predicting amyloid-positive patients in community-based cohorts is unclear. This study aimed to determine the predictive accuracy of Aβ precursor protein 669-711/Aβ1-42, Aβ1-40/1-42 and their composite biomarkers for brain amyloid deposition or the clinical progression in community-dwelling older adults with mild cognitive impairment (MCI).</p>\\n </section>\\n \\n <section>\\n \\n <h3> METHODS</h3>\\n \\n <p>This prospective cohort study was conducted from August 2015 to September 2019. Subsequently, the participants underwent follow-up cognitive assessments up to 8 years after the start of the study. Blood samples were collected from older adults aged ≥ 65 years with MCI at baseline. Plasma Aβ biomarkers were analyzed using immunoprecipitation-mass spectrometry. The accuracy of plasma biomarkers for brain amyloid status was evaluated using receiver operating characteristic curve analysis. Relationships between comorbidities and plasma Aβ 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‒Meier curves.</p>\\n </section>\\n \\n <section>\\n \\n <h3> RESULTS</h3>\\n \\n <p>The participants included 107 patients (57 [53.3%] females, median age: 76.0 [72.0–80.0] years). Plasma biomarkers correlated with cortical amyloid uptake (<i>ρ</i> = 0.667–0.754). 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 ε4 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, <i>P</i> < 0.001). The higher composite biomarker was associated with a faster rate of cognitive decline (<i>ρ</i> = −0.575, <i>P</i> < 0.001).</p>\\n </section>\\n \\n <section>\\n \\n <h3> DISCUSSION</h3>\\n \\n <p>Plasma Aβ composite biomarker may serve as a surrogate measure for amyloid deposition and a predictor of disease progression in a community-based cohort.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Highlights</h3>\\n \\n <div>\\n <ul>\\n \\n <li>Plasma amyloid beta (Aβ) biomarkers correlated with 11C-Pittsburgh compound B uptake, mainly in the frontal/parietotemporal cortices and posterior cingulate gyrus.</li>\\n \\n <li>The amyloid composite biomarker can predict amyloid positron emission tomography positivity with a high area under the curve of 0.943 in a community-based mild cognitive impairment cohort.</li>\\n \\n <li>The higher amyloid composite biomarker at baseline was significantly associated with worsening Mini-Mental State Examination score and a high risk for developing Alzheimer's disease (AD) dementia over 8 years.</li>\\n \\n <li>The amyloid composite biomarker can predict clinical progression to AD dementia with a high area under the curve of 0.860.</li>\\n \\n <li>Apolipoprotein E ε4 status influenced the plasma Aβ biomarker levels.</li>\\n </ul>\\n </div>\\n </section>\\n </div>\",\"PeriodicalId\":53225,\"journal\":{\"name\":\"Alzheimer''s and Dementia: Translational Research and Clinical Interventions\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.9000,\"publicationDate\":\"2024-10-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70008\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Alzheimer''s and Dementia: Translational Research and Clinical Interventions\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/trc2.70008\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/trc2.70008","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Plasma amyloid beta biomarkers predict amyloid positivity and longitudinal clinical progression in mild cognitive impairment
INTRODUCTION
Previous studies have examined the predictive accuracy of plasma amyloid beta (Aβ) biomarkers in clinical cohorts. However, their accuracy for predicting amyloid-positive patients in community-based cohorts is unclear. This study aimed to determine the predictive accuracy of Aβ precursor protein 669-711/Aβ1-42, Aβ1-40/1-42 and their composite biomarkers for brain amyloid deposition or the clinical progression in community-dwelling older adults with mild cognitive impairment (MCI).
METHODS
This prospective cohort study was conducted from August 2015 to September 2019. Subsequently, the participants underwent follow-up cognitive assessments up to 8 years after the start of the study. Blood samples were collected from older adults aged ≥ 65 years with MCI at baseline. Plasma Aβ biomarkers were analyzed using immunoprecipitation-mass spectrometry. The accuracy of plasma biomarkers for brain amyloid status was evaluated using receiver operating characteristic curve analysis. Relationships between comorbidities and plasma Aβ 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‒Meier curves.
RESULTS
The participants included 107 patients (57 [53.3%] females, median age: 76.0 [72.0–80.0] years). Plasma biomarkers correlated with cortical amyloid uptake (ρ = 0.667–0.754). 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 ε4 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, P < 0.001). The higher composite biomarker was associated with a faster rate of cognitive decline (ρ = −0.575, P < 0.001).
DISCUSSION
Plasma Aβ composite biomarker may serve as a surrogate measure for amyloid deposition and a predictor of disease progression in a community-based cohort.
Highlights
Plasma amyloid beta (Aβ) biomarkers correlated with 11C-Pittsburgh compound B uptake, mainly in the frontal/parietotemporal cortices and posterior cingulate gyrus.
The amyloid composite biomarker can predict amyloid positron emission tomography positivity with a high area under the curve of 0.943 in a community-based mild cognitive impairment cohort.
The higher amyloid composite biomarker at baseline was significantly associated with worsening Mini-Mental State Examination score and a high risk for developing Alzheimer's disease (AD) dementia over 8 years.
The amyloid composite biomarker can predict clinical progression to AD dementia with a high area under the curve of 0.860.
Apolipoprotein E ε4 status influenced the plasma Aβ biomarker levels.
期刊介绍：
Alzheimer''s & Dementia: Translational Research & Clinical Interventions (TRCI) is a peer-reviewed, open access,journal from the Alzheimer''s Association®. The journal seeks to bridge the full scope of explorations between basic research on drug discovery and clinical studies, validating putative therapies for aging-related chronic brain conditions that affect cognition, motor functions, and other behavioral or clinical symptoms associated with all forms dementia and Alzheimer''s disease. The journal will publish findings from diverse domains of research and disciplines to accelerate the conversion of abstract facts into practical knowledge: specifically, to translate what is learned at the bench into bedside applications. The journal seeks to publish articles that go beyond a singular emphasis on either basic drug discovery research or clinical research. Rather, an important theme of articles will be the linkages between and among the various discrete steps in the complex continuum of therapy development. For rapid communication among a multidisciplinary research audience involving the range of therapeutic interventions, TRCI will consider only original contributions that include feature length research articles, systematic reviews, meta-analyses, brief reports, narrative reviews, commentaries, letters, perspectives, and research news that would advance wide range of interventions to ameliorate symptoms or alter the progression of chronic neurocognitive disorders such as dementia and Alzheimer''s disease. The journal will publish on topics related to medicine, geriatrics, neuroscience, neurophysiology, neurology, psychiatry, clinical psychology, bioinformatics, pharmaco-genetics, regulatory issues, health economics, pharmacoeconomics, and public health policy as these apply to preclinical and clinical research on therapeutics.
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