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Alzheimer's Association International Conference 2026

July 12-15, 2026 | London, United Kingdom, and Online

9701

Diagnosis And Prognosis Of Alzheimer’s Disease Using CSF: Added Value Of aί40 And Making Use Of All Available Biomarkers

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Poster Presenter

Thomas Claessen

Authors

Thomas Claessen, Inge Verberk, Wiesje van der Flier, Afina Lemstra, Yolande Pijnenburg, Marleen Koel-Simmelink, Charlotte Teunissen, Argonde van Harten

Affiliations

Neurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands, Alzheimer Center Amsterdam, Department of Neurology, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands, Neurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands, Alzheimer Nederland, Amersfoort, the Netherlands, Epidemiology and Data Science, Vrije Universiteit Amsterdam, Amsterdam UMC, location VUmc, Amsterdam, Alzheimer Center Amsterdam, Department of Neurology, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands

Part of Topic

BACKGROUND

•Cerebrospinal fluid (CSF) pTau-181/Aβ42 and Aβ42/40 are widely used to detect Alzheimer’s disease (AD) pathology.

•pTau-181/Aβ42 combines amyloid and tau biomarkers, limiting independent A-T(-N) staging.

•Adding Aβ40 permits amyloid assessment with Aβ42/40 while preserving pTau-181 as an independent tau marker.

AIM

To investigate whether adding Aβ40 to Aβ42 and pTau-181 preserves concordance with amyloid positron emission tomography (PET) and improves prognostic stratification in a memory clinic cohort.

METHODS

Inclusion criteria

•Diagnostic: 448 individuals with available amyloid PET within one year of CSF collection (Table 1).

•Prognostic: 220 individuals with SCD and 290 with MCI and available longitudinal follow-up data (Table 2).

Biomarkers

•CSF Aβ40 was measured using the Elecsys® research-use-only assay, alongside Elecsys® Aβ42 and pTau-181 assays.

Analyses

•Diagnostic: Accuracy was assessed using receiver operating characteristic curves with amyloid PET status as reference.

•Prognostic: Clinical progression was analyzed using Cox proportional hazards models. Gaussian mixture modeling identified low, intermediate, and high pTau-181 stages to assess whether pTau-181 stratification predicted progression beyond amyloid positivity.

DIAGNOSTIC RESULTS

Aβ42/40 and pTau-181/Aβ42 detected amyloid PET positivity with similar accuracy (p>0.05, Figure 1).

PROGNOSTIC RESULTS

pTau-181/Aβ42 (SCD HR 6.42, MCI HR 4.44) and Aβ42/40 (SCD HR 6.11, MCI HR 4.19, Figure 2.A) were similarly associated with clinical progression.

Among Aβ42/40-positive individuals, increasing pTau-181 stages were associated with increases in progression risk (SCD HR 4.40, 7.37, and 16.9; MCI HR 3.20, 4.50, and 6.74 for low, intermediate, and high pTau-181, Figure 2.C).

CONCLUSION

•The Aβ42/40 ratio and the pTau-181/Aβ42 ratio showed similar diagnostic performance for detecting amyloid PET positivity.

•Adding Aβ40 enabled separate amyloid and tau classification, supporting more granular prognostic stratification in amyloid-positive individuals with SCD and MCI.

ACKNOWLEDGEMENTS

We thank Roche Diagnostics for providing all Elecsys® assay kits used in this study free of charge.

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