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. 2023;93(4):1537-1549.
doi: 10.3233/JAD-221187.

Elecsys Cerebrospinal Fluid Immunoassays Accurately Detect Alzheimer's Disease Regardless of Concomitant Small Vessel Disease

Marion Ortner  1 , Korbinian Lanz  1 , Oliver Goldhardt  1 , Felix Müller-Sarnowski  1 , Janine Diehl-Schmid  1 , Hans Förstl  1 , Dennis M Hedderich  2 , Igor Yakushev  3 , Chad A Logan  4 , Jan-Philipp Weinberger  4 , Maryline Simon  5 , Timo Grimmer  1
Affiliations

Elecsys Cerebrospinal Fluid Immunoassays Accurately Detect Alzheimer's Disease Regardless of Concomitant Small Vessel Disease

Marion Ortner et al. J Alzheimers Dis. 2023.

Abstract

Background: Differentiating dementia due to small vessel disease (SVD) from dementia due to Alzheimer's disease (AD) with concomitant SVD is challenging in clinical practice. Accurate and early diagnosis of AD is critical to delivering stratified patient care.

Objective: We characterized the results of Elecsys® cerebrospinal fluid (CSF) immunoassays (Roche Diagnostics International Ltd) in patients with early AD, diagnosed using core clinical criteria, with varying extent of SVD.

Methods: Frozen CSF samples (n = 84) were measured using Elecsys β-Amyloid(1-42) (Aβ42), Phospho-Tau (181P) (pTau181), and Total-Tau (tTau) CSF immunoassays, adapted for use on the cobas® e 411 analyzer (Roche Diagnostics International Ltd), and a robust prototype β-Amyloid(1-40) (Aβ40) CSF immunoassay. SVD was assessed by extent of white matter hyperintensities (WMH) using the lesion segmentation tool. Interrelations between WMH, biomarkers, fluorodeoxyglucose F18-positron emission tomography (FDG-PET), and other parameters (including age and Mini-Mental State examinations [MMSE]) were assessed using Spearman's correlation, sensitivity/specificity, and logistic/linear regression analyses.

Results: The extent of WMH showed significant correlation with Aβ42/Aβ40 ratio (Rho=-0.250; p = 0.040), tTau (Rho = 0.292; p = 0.016), tTau/Aβ42 ratio (Rho = 0.247; p = 0.042), age (Rho = 0.373; p = 0.002), and MMSE (Rho=-0.410; p = 0.001). Sensitivity/specificity point estimates for Elecsys CSF immunoassays versus FDG-PET positivity for underlying AD pathophysiology were mostly comparable or greater in patients with high versus low WMH. WMH were not a significant predictor and did not interact with CSF biomarker positivity but modified the association between pTau181 and tTau.

Conclusion: Elecsys CSF immunoassays detect AD pathophysiology regardless of concomitant SVD and may help to identify patients with early dementia with underlying AD pathophysiology.

Keywords: Alzheimer’s disease; biomarkers; cerebral small vessel diseases; cerebrospinal fluid; diagnosis; differential.

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Conflict of interest statement

JD-S is an Editorial Board Member of this journal but was not involved in the peer-review process nor had access to any information regarding its peer-review. CL and JPW are employees of Roche Diagnostics GmbH and hold shares in F. Hoffmann-La Roche Ltd. MS is a former employee of Roche Diagnostics International Ltd. The remaining authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript.

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