Effects of obesity on plasma biomarker and amyloid PET trajectories in Alzheimer's disease.

IF 4.4 Q1 CLINICAL NEUROLOGY
Soheil Mohammadi, Farzaneh Rahmani, Mahsa Dolatshahi, Suzanne E Schindler, Cyrus A Raji
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引用次数: 0

Abstract

Introduction: Obesity is a risk factor for Alzheimer's disease (AD), but its impact on AD blood biomarker (BBM) and amyloid positron emission tomography (PET) trajectories is unknown.

Methods: One thousand two hundred twenty-eight plasma samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were assessed using six leading commercial tests (C2N, Fujirebio, Janssen, ALZpath, Roche, and Quanterix). Amyloid PET scans were used to assess amyloid burden in Centiloids (CLs). Spearman partial correlations assessed cross-sectional associations, while linear mixed-effects models examined the longitudinal impact of obesity status on BBMs and CLs.

Results: Higher body mass index at baseline was correlated with lower levels of plasma phosphorylated tau (p-tau)217, p-tau217 ratio, neurofilament light chain (NfL), glial fibrillary acidic protein, and CLs. However, baseline obesity predicted higher rate of increase in p-tau217, p-tau217 ratio, Roche NfL, and amyloid PET burden over time.

Discussion: This study provides insights for longitudinal changes in AD pathologies, as measured by BBM levels and CLs, in association with obesity.

Highlights: Higher body mass index was related to lower baseline plasma tau phosphorylated at threonine 217 (p-tau217), p-tau217, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) and amyloid positron emission tomography (PET) burden.Obesity predicts a faster increase in p-tau217, p-tau217 ratio, and NfL.Obesity predicts a faster increase in amyloid PET burden.Changes in GFAP over time are not linked with obesity.

Abstract Image

Abstract Image

肥胖对阿尔茨海默病血浆生物标志物和淀粉样蛋白PET轨迹的影响
肥胖是阿尔茨海默病(AD)的危险因素,但其对AD血液生物标志物(BBM)和淀粉样正电子发射断层扫描(PET)轨迹的影响尚不清楚。方法:使用六种领先的商业测试(C2N、Fujirebio、Janssen、ALZpath、Roche和Quanterix)对来自阿尔茨海默病神经影像学倡议(ADNI)的1228份血浆样本进行评估。淀粉样蛋白PET扫描用于评估Centiloids (CLs)的淀粉样蛋白负荷。Spearman偏相关评估了横断面关联,而线性混合效应模型检查了肥胖状况对脑卒中和慢性淋巴细胞的纵向影响。结果:基线时较高的体重指数与较低的血浆磷酸化tau (p-tau)217、p-tau217比率、神经丝轻链(NfL)、胶质纤维酸性蛋白和CLs水平相关。然而,随着时间的推移,基线肥胖预测p-tau217、p-tau217比率、Roche NfL和淀粉样PET负担的增加率更高。讨论:该研究提供了与肥胖相关的AD病理的纵向变化,通过BBM水平和CLs测量。重点:较高的体重指数与较低的基线血浆tau蛋白在苏氨酸217 (p-tau217)、p-tau217、神经丝轻链(NfL)、胶质纤维酸性蛋白(GFAP)和淀粉样正电子发射断层扫描(PET)负荷下磷酸化有关。肥胖预示着p-tau217、p-tau217比值和NfL的更快增长。肥胖预示着淀粉样蛋白PET负担增加更快。GFAP随时间的变化与肥胖无关。
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来源期刊
CiteScore
7.80
自引率
7.50%
发文量
101
审稿时长
8 weeks
期刊介绍: Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.
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