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Kurz, Carolin ORCID logoORCID: https://orcid.org/0000-0003-4299-6240; Carli, Laura; Gürsel, Selim Üstün ORCID logoORCID: https://orcid.org/0000-0001-6714-5827; Schrurs, Isabelle; Jethwa, Alexander; Carboni, Margherita; Bittner, Tobias; Hortsch, Sayuri; Keeser, Daniel ORCID logoORCID: https://orcid.org/0000-0002-0244-1024; Brendel, Matthias ORCID logoORCID: https://orcid.org/0000-0002-9247-2843; Burow, Lena; Haeckert, Jan; Koriath, Carolin A. M.; Tatò, Maia; Utecht, Julia; Papazov, Boris ORCID logoORCID: https://orcid.org/0000-0002-5274-9166; Morenas-Rodriguez, Estrella; Pogarell, Oliver ORCID logoORCID: https://orcid.org/0000-0001-6455-4190; Palleis, Carla ORCID logoORCID: https://orcid.org/0000-0002-4331-8145; Weidinger, Endy; Stoecklein, Sophia ORCID logoORCID: https://orcid.org/0000-0003-0325-4674; Levin, Johannes ORCID logoORCID: https://orcid.org/0000-0001-5092-4306; Höglinger, Günter ORCID logoORCID: https://orcid.org/0000-0001-7587-6187; Rauchmann, Boris-Stephan ORCID logoORCID: https://orcid.org/0000-0003-4547-6240 und Perneczky, Robert ORCID logoORCID: https://orcid.org/0000-0003-1981-7435 (2025): Plasma biomarkers of amyloid, tau & neuroinflammation in Alzheimer’s disease and corticobasal syndrome. In: European Archives of Psychiatry and Clinical Neuroscience [Forthcoming]

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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.

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