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Background <p>Blood-based biomarkers (BBBMs) could significantly facilitate the diagnosis of Alzheimer’s disease (AD) and non-AD dementia by providing less invasive alternatives to cerebrospinal fluid (CSF) and positron emission tomography (PET) imaging.</p> Objective <p>This study investigated how well the BBBMs—amyloid-β (Aβ) 1-42/1-40 ratio, phosphorylated tau181 (pTau181), apolipoprotein E4 (ApoE4), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL)—reflect thorough clinical work-up validated by PET and CSF biomarkers in participants with AD (n = 27), Aβ-negative CBS (n = 26), and agematched healthy controls (HC) (n = 17).</p> Methods <p>Factor and correlation explored biomarker associations. Bayesian regression, backward selection regression, and ROC curve analysis were applied to identify optimal biomarker combinations and diagnostic cut-offs.</p> Results <p>In AD cases, pTau181 and ApoE4 levels were elevated, and the Aβ1-42/1-40 ratio was reduced. ROC analysis showed high accuracy for pTau181, ApoE4 and Aβ1-42/1-40 in discriminating AD from HC, with a combination significantly improving performance. However, limited fold change, and high variability reduced the diagnostic applicability of Aβ1-42/1-40 ratio. Elevated NfL levels were the most reliable biomarker for CBS-Aβ(–) cases. GFAP showed limited discriminatory power due to overlapping levels, suggesting that it may not serve as a disease-specific biomarker but may be indicative of general neurodegeneration.</p> Conclusions <p> This study highlights the diagnostic utility of pTau181, ApoE4 and the Aβ1-42/1-40 ratio for AD and NfL in the CBS-Aβ(–) cases and emphasizes the added value of combined biomarker models for group differentiation. Prospective studies will help validate these findings and refine clinical thresholds.</p>

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Plasma biomarkers of amyloid, tau & neuroinflammation in Alzheimer’s disease and corticobasal syndrome

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月2日

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  • Carolin Kurz,
  • Laura Carli,
  • Selim Üstün Gürsel,
  • Isabelle Schrurs,
  • Alexander Jethwa,
  • Margherita Carboni,
  • Tobias Bittner,
  • Sayuri Hortsch,
  • Daniel Keeser,
  • Matthias Brendel,
  • Lena Burow,
  • Jan Haeckert,
  • Carolin A. M. Koriath,
  • Maia Tatò,
  • Julia Utecht,
  • Boris Papazov,
  • Estrella Morenas-Rodriguez,
  • Oliver Pogarell,
  • Carla Palleis,
  • Endy Weidinger,
  • Sophia Stoecklein,
  • Johannes Levin,
  • Günter Höglinger,
  • Boris-Stephan Rauchmann,
  • Robert Perneczky

摘要

Background

Blood-based biomarkers (BBBMs) could significantly facilitate the diagnosis of Alzheimer’s disease (AD) and non-AD dementia by providing less invasive alternatives to cerebrospinal fluid (CSF) and positron emission tomography (PET) imaging.

Objective

This study investigated how well the BBBMs—amyloid-β (Aβ) 1-42/1-40 ratio, phosphorylated tau181 (pTau181), apolipoprotein E4 (ApoE4), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL)—reflect thorough clinical work-up validated by PET and CSF biomarkers in participants with AD (n = 27), Aβ-negative CBS (n = 26), and agematched healthy controls (HC) (n = 17).

Methods

Factor and correlation explored biomarker associations. Bayesian regression, backward selection regression, and ROC curve analysis were applied to identify optimal biomarker combinations and diagnostic cut-offs.

Results

In AD cases, pTau181 and ApoE4 levels were elevated, and the Aβ1-42/1-40 ratio was reduced. ROC analysis showed high accuracy for pTau181, ApoE4 and Aβ1-42/1-40 in discriminating AD from HC, with a combination significantly improving performance. However, limited fold change, and high variability reduced the diagnostic applicability of Aβ1-42/1-40 ratio. Elevated NfL levels were the most reliable biomarker for CBS-Aβ(–) cases. GFAP showed limited discriminatory power due to overlapping levels, suggesting that it may not serve as a disease-specific biomarker but may be indicative of general neurodegeneration.

Conclusions

This study highlights the diagnostic utility of pTau181, ApoE4 and the Aβ1-42/1-40 ratio for AD and NfL in the CBS-Aβ(–) cases and emphasizes the added value of combined biomarker models for group differentiation. Prospective studies will help validate these findings and refine clinical thresholds.