Characterization of plasma AT(N) biomarkers among a racial and ethnically diverse community-based cohort: an HABS-HD study

IF 4.9 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Pub Date : 2025-02-19 DOI:10.1002/trc2.70045

Melissa E. Petersen, Fan Zhang, James Hall, Courtney Brock, Robert A. Rissman, Tori Como, David Julovich, Mark Mapstone, Beau M. Ances, Karin Meeker, Raymond Palmer, Robert Barber, David Mason, Leigh Johnson, Kristine Yaffe, Arthur W. Toga, Annie Cohen, Sid E. O'Bryant, for the HABS-HD Study Team

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引用次数: 0

Abstract

INTRODUCTION

Alzheimer's disease (AD) biomarkers of Amyloid(A), Tau(T), and Neurodegeneration(N) have been increasingly studied to fill the gap in our understanding of racial and ethnic differences. This study aimed to examine the relationship between plasma AT(N) biomarkers and (1) AT(N) neuroimaging biomarkers, (2) demographics, (3) medical comorbidities, and (4) cognitive diagnosis.

METHODS

Data were analyzed from n = 764 non-Hispanic Black (NHB), n = 1230 Hispanic, and n = 1232 non-Hispanic White (NHW) participants. Plasma AT(N) biomarkers were derived using single molecule array (SIMOA) technology on an HD-X imager and included amyloid beta (Aβ)42/40, total tau, ptau181, and neurofilament light chain (NfL). Clinical reads of positron emission tomography (PET) amyloid and tau positivity were used to examine the link between AT(N) plasma and neuroimaging biomarkers. Generalized linear models were conducted to examine the relationship between plasma AT(N) biomarkers and select demographic, diagnostic, and medical comorbidities (hypertension, diabetes, dyslipidemia, chronic kidney disease).

RESULTS

Differences in the AT(N) biomarkers were found across racial/ethnic groups. Plasma Aβ42/40 was found to be associated with PET amyloid positivity only among NHW participants, while plasma NfL was found to correlate with Meta-ROI among NHB and Hispanic participants. Ptau181 was associated with PET amyloid positivity among NHB and NHW participants and well as PET tau positivity among the latter group and Hispanic participants. Diabetes was related to increased plasma AT(N) biomarkers among NHB and Hispanic participants. CKD was associated with increased AT(N) biomarkers for all race/ethnic groups with the exception of Aβ42/40. While Aβ42/40, total tau, ptau181, and NfL were found to be related to a dementia diagnosis among NHW participants, only ptau181 and NfL were found to be related to this same diagnostic category among NHB and Hispanic participants.

DISCUSSION

Our findings indicate differential relationships between comorbidities (demographic, medical, diagnostic) across NHB, Hispanic, and NHW participants. This work expands our knowledge regarding the associations of plasma biomarkers to AD pathology in diverse populations.

Highlights

Differences in AT(N) plasma biomarkers were found in a diverse community cohort.
While plasma Aβ42/40 was associated with PET amyloid positivity among non-Hispanic white participants, this did not apply to non-Hispanic Black or Hispanic participants.
Medical comorbidity of diabetes and chronic kidney disease was related to increased plasma AT(N) biomarkers among the ethnically diverse segment of the cohort.
Plasma AT(N) biomarkers were more so related to a diagnosis of dementia for non-Hispanic white as compared to Hispanic or non-Hispanic Black participants.
Across racial/ethnic groups, the plasma biomarkers of neurodegeneration (NfL) and ptau181 were related to a diagnosis of dementia.

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在一个种族和民族多样化的社区队列中血浆AT(N)生物标志物的特征：一项HABS-HD研究

阿尔茨海默病（AD）的淀粉样蛋白(A)、Tau蛋白(T)和神经变性(N)生物标志物的研究越来越多，以填补我们对种族和民族差异理解的空白。本研究旨在探讨血浆AT(N)生物标志物与(1)AT(N)神经成像生物标志物、(2)人口统计学、(3)医学合并症和(4)认知诊断之间的关系。方法分析n = 764名非西班牙裔黑人（NHB）、n = 1230名西班牙裔和n = 1232名非西班牙裔白人（NHW）参与者的数据。在HD-X成像仪上使用单分子阵列（SIMOA）技术获得血浆AT(N)生物标志物，包括β淀粉样蛋白（Aβ）42/40、总tau蛋白、ptau181和神经丝轻链（NfL）。使用正电子发射断层扫描（PET）淀粉样蛋白和tau阳性的临床读数来检查AT(N)血浆与神经成像生物标志物之间的联系。采用广义线性模型来检验血浆AT(N)生物标志物与选择的人口统计学、诊断和医学合并症（高血压、糖尿病、血脂异常、慢性肾病）之间的关系。结果AT(N)生物标志物在不同种族/民族间存在差异。血浆Aβ42/40仅在NHW参与者中与PET淀粉样蛋白阳性相关，而血浆NfL与NHB和西班牙裔参与者的Meta-ROI相关。Ptau181与NHB和NHW参与者的PET淀粉样蛋白阳性以及后者和西班牙裔参与者的PET tau蛋白阳性相关。在NHB和西班牙裔参与者中，糖尿病与血浆AT(N)生物标志物升高有关。除Aβ42/40外，CKD与所有种族/民族的AT(N)生物标志物升高有关。虽然在NHW参与者中发现a β42/40、总tau、ptau181和NfL与痴呆诊断相关，但在NHB和西班牙裔参与者中发现只有ptau181和NfL与相同的诊断类别相关。讨论：我们的研究结果表明，NHB、西班牙裔和NHW参与者的合并症（人口统计学、医学、诊断）之间存在差异关系。这项工作扩大了我们对血浆生物标志物与不同人群阿尔茨海默病病理关系的认识。在不同的社区队列中发现了AT(N)血浆生物标志物的差异。虽然血浆Aβ42/40与非西班牙裔白人参与者的PET淀粉样蛋白阳性有关，但这并不适用于非西班牙裔黑人或西班牙裔参与者。在不同种族的人群中，糖尿病和慢性肾脏疾病的医学合并症与血浆AT(N)生物标志物的增加有关。与西班牙裔或非西班牙裔黑人受试者相比，血浆AT(N)生物标志物与非西班牙裔白人痴呆诊断的相关性更大。在不同种族/民族的人群中，血浆生物标志物神经变性（NfL）和ptau181与痴呆的诊断有关。

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来源期刊

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Medicine-Psychiatry and Mental Health

CiteScore

10.10

自引率

2.10%

发文量

134

审稿时长

10 weeks

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.