Blood biomarkers for Alzheimer's disease: Reliable change and impacts of renal and blood-brain barrier function.

IF 4.4 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2025-09-08 eCollection Date: 2025-07-01 DOI:10.1002/dad2.70181

Anders Behrens, Peter Anderberg, Johan Sanmartin Berglund, Malena Cianchetta-Sivoriceruti, Ana Luiza Dallora

{"title":"Blood biomarkers for Alzheimer's disease: Reliable change and impacts of renal and blood-brain barrier function.","authors":"Anders Behrens, Peter Anderberg, Johan Sanmartin Berglund, Malena Cianchetta-Sivoriceruti, Ana Luiza Dallora","doi":"10.1002/dad2.70181","DOIUrl":null,"url":null,"abstract":"Introduction: Blood-based biomarkers for Alzheimer's disease (AD) have the potential to improve diagnostic accessibility, but their clinical interpretation requires understanding of variability and biological influences.Methods: We repeatedly sampled blood from 57 adults referred for lumbar puncture as part of a cognitive evaluation at a memory clinic. We measured serum phosphorylated- tau-181 (s-p-tau181) and plasma amyloid beta (Aβ)42/40 ratio (p-Aβ42/Aβ40) and evaluated the impact of renal and blood-brain barrier (BBB) function.Results: Test-retest analysis revealed large variability of s-p-tau181 and small for p-Aβ42/Aβ40. Markers of renal function and BBB integrity significantly influenced s-p-tau181 levels, whereas p-Aβ42/Aβ40 was not affected.Discussion: This study emphasizes the need for caution when interpreting longitudinal changes in s-p-tau181. Inter-individual variability is to a large degree due to susceptibility to biological influences where a novel association with integrity of BBB function were identified. These results have implications for the clinical application of blood-based biomarkers in AD diagnostics and monitoring.Highlights: Blood phosphorylated- tau-181 (p-tau181) shows high test-retest variability in memory clinic patients.Blood amyloid beta (Aβ)42/Aβ40 ratio is stable but has poor diagnostic accuracy.Renal function and blood-brain barrier (BBB) integrity affect blood p-tau181 levels.Caution is needed when interpreting longitudinal changes in blood p-tau181.Renal and BBB disorders should be considered when assessing blood p-tau181.","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"17 3","pages":"e70181"},"PeriodicalIF":4.4000,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12417335/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/dad2.70181","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction: Blood-based biomarkers for Alzheimer's disease (AD) have the potential to improve diagnostic accessibility, but their clinical interpretation requires understanding of variability and biological influences.

Methods: We repeatedly sampled blood from 57 adults referred for lumbar puncture as part of a cognitive evaluation at a memory clinic. We measured serum phosphorylated- tau-181 (s-p-tau181) and plasma amyloid beta (Aβ)42/40 ratio (p-Aβ42/Aβ40) and evaluated the impact of renal and blood-brain barrier (BBB) function.

Results: Test-retest analysis revealed large variability of s-p-tau181 and small for p-Aβ42/Aβ40. Markers of renal function and BBB integrity significantly influenced s-p-tau181 levels, whereas p-Aβ42/Aβ40 was not affected.

Discussion: This study emphasizes the need for caution when interpreting longitudinal changes in s-p-tau181. Inter-individual variability is to a large degree due to susceptibility to biological influences where a novel association with integrity of BBB function were identified. These results have implications for the clinical application of blood-based biomarkers in AD diagnostics and monitoring.

Highlights: Blood phosphorylated- tau-181 (p-tau181) shows high test-retest variability in memory clinic patients.Blood amyloid beta (Aβ)42/Aβ40 ratio is stable but has poor diagnostic accuracy.Renal function and blood-brain barrier (BBB) integrity affect blood p-tau181 levels.Caution is needed when interpreting longitudinal changes in blood p-tau181.Renal and BBB disorders should be considered when assessing blood p-tau181.

Abstract Image

查看原文本刊更多论文

阿尔茨海默病的血液生物标志物：肾和血脑屏障功能的可靠变化和影响。

基于血液的阿尔茨海默病（AD）生物标志物具有提高诊断可及性的潜力，但其临床解释需要了解变异性和生物学影响。方法：我们反复抽取57名成年人的血液样本，作为记忆诊所认知评估的一部分，他们接受腰椎穿刺治疗。我们测量了血清磷酸化- tau-181 （s-p-tau181）和血浆β淀粉样蛋白（Aβ）42/40比值（p-Aβ42/Aβ40），并评估了肾和血脑屏障（BBB）功能的影响。结果：重测分析显示s-p-tau181变异较大，而p- a - β42/ a - β40变异较小。肾功能和血脑屏障完整性标志物显著影响s-p-tau181水平，而p- a - β42/ a - β40不受影响。讨论：本研究强调在解释s-p-tau1的纵向变化时需要谨慎。个体间差异在很大程度上是由于生物影响的易感性，其中发现了与血脑屏障功能完整性的新关联。这些结果对基于血液的生物标志物在AD诊断和监测中的临床应用具有重要意义。重点：血液磷酸化- tau-181 （p-tau181）在记忆临床患者中显示出很高的重测变异性。血β淀粉样蛋白（Aβ）42/Aβ40比值稳定，但诊断准确性差。肾功能和血脑屏障（BBB）完整性影响血液p-tau181水平。在解释血液中p-tau181的纵向变化时需要谨慎。在评估血液p-tau181时应考虑肾脏和血脑屏障疾病。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Medicine-Psychiatry and Mental Health

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.