Elecsys Cerebrospinal Fluid Assays Accurately Distinguish Alzheimer's Disease from Frontotemporal Lobar Degeneration

Background Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) are heterogeneous in their clinical presentation and underlying pathology, but they often have overlapping features. Diagnostic accuracy is critical for guiding patient management. Cerebrospinal fluid (CSF) diagnostic assays for the differentiation of AD and FTLD may increase diagnostic accuracy. Objectives In this study, we aimed to understand the potential role of CSF biomarkers and biomarker ratios, measured using Elecsys (R) CSF immunoassays (Roche Diagnostics International Ltd, Rotkreuz, Switzerland), in the differential diagnosis of AD and FTLD. Design This study was conducted at a single center in Munich, Germany between July 2019 and July 2020. Patient CSF samples were retrospectively collected from the study center biobank. Participants A total of 130 patients with cognitive impairment were included in the study; 86 patients were diagnosed with AD and 44 with FTLD (behavioral variant frontotemporal dementia, semantic variant of primary progressive aphasia, and non-fluent variant of primary progressive aphasia), based on core clinical criteria and a non-CSF biomarker, a typical pattern of regional hypometabolism on [F-18] fluorodeoxyglucose positron emission tomography. Measurements Patient CSF biomarker concentrations were measured using Elecsys CSF immunoassays. Receiver operating characteristic analyses were conducted to determine areas under the curve (AUCs) for CSF biomarker performance. Sensitivity and specificity analyses were conducted to evaluate the performance of established cut-offs (A beta 42 <= 1000 pg/mL, pTau181/A beta 42 ratio >0.024, and tTau/A beta 42 ratio >0.28) and optimized cut-offs based on Youden's index. Results AUC-based performance was similarly good for the pTau181/A beta 42 ratio (AUC=0.841; 95% CI: 0.759-0.923), pTau181/A beta 40 ratio (AUC=0.837; 95% CI: 0.754-0.919), A beta 42/A beta 40 ratio (AUC=0.829; 95% CI: 0.746-0.912), tTau/A beta 42 ratio (AUC=0.822; 95% CI: 0.736-0.908), pTau181/A beta 42/A beta 40 ratio (AUC=0.817; 95% CI: 0.734-0.901), and A beta 42 (AUC=0.812; 95% CI: 0.722-0.902). Performance was slightly lower for the tTau/A beta 42/A beta 40 ratio (AUC=0.799; 95% CI: 0.713-0.885), pTau181 alone (AUC=0.793; 95% CI: 0.707-0.880), tTau/A beta 40 ratio (AUC=0.751; 95% CI: 0.657-0.844), and tTau alone (AUC=0.706; 95% CI: 0.613-0.799). The highest qualitative performance was observed with the pTau181/A beta 42 ratio with an established cut-off value of >0.024 and optimized cut-off value of >0.022: sensitivity and specificity values were 0.892 and 0.773, respectively. Conclusions Elecsys CSF immunoassays demonstrate good diagnostic accuracy in differentiating patients with AD from those with FTLD. These immunoassays have the potential to support clinical decision making, i.e. in diagnosing patients with FTLD by excluding patients with amyloid positivity, which is indicative of underlying AD.