European archives of psychiatry and clinical neuroscience · 2025
Plasma biomarkers of amyloid, tau & neuroinflammation in Alzheimer's disease and corticobasal syndrome.
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Kurz Carolin, Carli Laura, Gürsel Selim Üstün, Schrurs Isabelle, Jethwa Alexander, Carboni Margherita, Bittner Tobias, Hortsch Sayuri, Keeser Daniel, Brendel Matthias, Burow Lena, Haeckert Jan, Koriath Carolin A M, Tatò Maia, Utecht Julia, Papazov Boris, Morenas-Rodriguez Estrella, Pogarell Oliver, Palleis Carla, Weidinger Endy, Stoecklein Sophia, Levin Johannes, Höglinger Günter, Rauchmann Boris-Stephan, Perneczky Robert
Аннотация
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.
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.