The solely A+ CSF Aβ42/40 ratio using Elecsys® assays performs similar to A/T and A/N ratios in predicting amyloid PET positivity: Developing topics. (7th December 2020)

• Record Type: Journal Article
• Authors: Grimmer, Timo; Amft, Michaela; Ortner, Marion; Eichenlaub, Udo; Goldhardt, Oliver; Müller‐Sarnowski, Felix; Diehl‐Schmid, Janine; Förstl, Hans; Yakushev, Igor
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 5
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.046988
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: pTau181/Aβ42 (A + /T + as per A/T/(N) classification) and tTau/Aβ42 (A + /(N) + ) ratios using fully automated Elecsys ® cerebrospinal‐fluid (CSF) immunoassays have been shown to perform well in distinguishing amyloid‐positivity (A + ) by positron emission tomography (PET) among patients with subjective and mild to severe cognitive impairment. Higher performance has also been demonstrated for the CSF Aβ42/40 ratio compared to CSF amyloid 42 (Aβ42) alone. We aimed to further evaluate the performance of the Elecsys ® Aβ42/40 ratio in a clinical cohort. Methods: Frozen (‐80°C) CSF samples from 103 patients treated in the Centre for Cognitive Disorders, Technical University of Munich were selected based on availability of visual amyloid‐PET status (n=54 PET+; 49 PET‐) determined during standard treatment around the time of CSF collection. In total, 71 patients were undergoing treatment for mild cognitive impairment (MCI) (n=44) or mild to moderate dementia (n=27) due to Alzheimer's disease (AD) and 32 patients for non‐AD related fronto‐temporal lobar degeneration (n=17), MCI (n=8), depression (n=5), alcohol dependence (n=1), or subjective cognitive impairment (SCD) (n=1). CSF was measured using Elecsys ® assays. CSF status for Aβ42, pTau181/Aβ42, and tTau/Aβ42 CSF (positive/negative) was determined based on pre‐defined biomarker cutoffs previously established using a different pre‐analytical protocol in MCI/SCD patients with suspected AD (CSF positive if Aβ42<1000 pg/ml, pTau181/Aβ42>0.024, and tTau/Aβ42>0.028). Sensitivity and specificity were calculated for CSF‐cutoff‐based status and ROC analysis was performed to determine AUC each versus visual amyloid‐PET status. Results: Pre‐defined biomarker thresholds were considered off‐label due to deviation from recommended sample collection protocol and storage parameters. Point estimates for sensitivity and specificity for each biomarker were; CSF Aβ42 alone (sensitivity = 0.93, specificity = 0.57), pTau181/Aβ42 (0.96, 0.69), and tTau/Aβ42 (0.92, 0.69). For AUC point estimates (95% confidence interval) were; CSF Aβ42 alone [0.78 (0.68‐0.88)], pTau181/Aβ42 [0.88 (0.81‐0.95)], tTau/Aβ42 [0.87(0.80‐0.95)], and Aβ42/40 [0.90 (0.83‐0.95)]. Conclusion: Fully automated Elecsys ® cerebrospinal fluid (CSF) immunoassay predicted amyloid positivity with high accuracy. In this study, the solely A + marker CSF Aβ42/40 ratio outperformed Aβ42 alone and performed similarly to Tau ratios. These results support those of previous studies showing high performance for the non‐Tau marker CSF Aβ42/40.