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

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 und Perneczky, Robert (2025): Plasma biomarkers of amyloid, tau & neuroinflammation in Alzheimer’s disease and corticobasal syndrome. In: European Archives of Psychiatry and Clinical Neuroscience [Forthcoming]

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy) ; Medizin > Klinikum der LMU München > Neurologische Klinik und Poliklinik mit Friedrich-Baur-Institut ; Medizin > Klinikum der LMU München > Klinik und Poliklink für Psychiatrie und Psychotherapie ; Medizin > Klinikum der LMU München > Klinik und Poliklinik für Radiologie
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0940-1334
• Bemerkung: Online first
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198