A Combination of Neurofilament Light, Glial Fibrillary Acidic Protein, and Neuronal Pentraxin-2 Discriminates Between Frontotemporal Dementia and Other Dementias.

BACKGROUND: The differential diagnosis of frontotemporal dementia (FTD) is still a challenging task due to its symptomatic overlap with other neurological diseases and the lack of biofluid-based biomarkers. OBJECTIVE: To investigate the diagnostic potential of a combination of novel biomarkers in cerebrospinal fluid (CSF) and blood. METHODS: We included 135 patients from the Center for Memory Disturbances, University of Perugia, with the diagnoses FTD (n = 37), mild cognitive impairment due to Alzheimer's disease (MCI-AD, n = 47), Lewy body dementia (PDD/DLB, n = 22), and cognitively unimpaired patients as controls (OND, n = 29). Biomarker levels of neuronal pentraxin-2 (NPTX2), neuronal pentraxin receptor, neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) were measured in CSF, as well as NfL and GFAP in serum. We assessed biomarker differences by analysis of covariance and generalized linear models (GLM). We performed receiver operating characteristics analyses and Spearman correlation to determine biomarker associations. RESULTS: CSF NPTX2 and serum GFAP levels varied most between diagnostic groups. The combination of CSF NPTX2, serum NfL and serum GFAP differentiated FTD from the other groups with good accuracy (FTD versus MCI-AD: area under the curve (AUC) [95% CI] = 0.89 [0.81-0.96]; FTD versus PDD/DLB: AUC = 0.82 [0.71-0.93]; FTD versus OND: AUC = 0.80 [0.70-0.91]). CSF NPTX2 and serum GFAP correlated positively only in PDD/DLB (ρ= 0.56, p < 0.05). NPTX2 and serum NfL did not correlate in any of the diagnostic groups. Serum GFAP and serum NfL correlated positively in all groups (ρ= 0.47-0.74, p < 0.05). CONCLUSION: We show the combined potential of CSF NPTX2, serum NfL, and serum GFAP to differentiate FTD from other neurodegenerative disorders.

Diagnostic performance of a fully automated chemiluminescent enzyme immunoassay for Alzheimer's disease diagnosis.

The variability of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers (Aß42, t-Tau and p-Tau) undermines their full-fledged introduction into routine diagnostics and clinical trials. The introduction of automatic systems can improve the diagnostic performance promoting standardization and reducing the impact of preanalytical and analytical factors. Here we assessed the diagnostic performance of a fully automated chemiluminescent enzyme assay (LUMIPULSE) and compared it with that obtained by using the classical manual enzyme-linked immunosorbent assays (ELISAs). Patients were clinically diagnosed as AD (n = 42) and non-AD (n = 38). Clinical diagnosis was confirmed at follow-up. LUMIPULSE Aß42 was reduced in AD (969.4 ±â€¯329.6 pg/mL vs. 1625.9 ±â€¯745.9 pg/mL, p <0.001), whereas LUMIPULSE t-Tau was increased in AD (768.2 ±â€¯281.0 pg/mL vs. 337.5 ±â€¯159.1 pg/mL, p < 0.001) compared to non-AD patients. Both LUMIPULSE Aß42 (AUC = 0.78, spec. = 0.74, sens. = 0.76) and t-Tau (AUC = 0.94, spec. = 0.93, sens. = 0.87) showed good accuracy in distinguish AD from non-AD and a high correlation with the manual ELISAs (r = 0.87, p < 0.001 and r = 0.92, p < 0.001, respectively). LUMIPULSE improves clinical accuracy in AD diagnosis, promoting the use of standardized values for CSF biomarkers with a good correlation with classical manual assays.