Cerebrospinal Fluid Biomarkers in Patients with Frontotemporal Dementia Spectrum: A Single-Center Study.

Abstract

Cerebrospinal fluid (CSF) neurofilament light chain protein (NfL) and Alzheimer's disease (AD) core biomarker levels have been evaluated in cohorts of patients with frontotemporal dementia spectrum (FTD), but the distribution of values across the different clinical syndromes and underlying proteinopathies, and the relative diagnostic accuracy appear discordant among studies. We measured CSF NfL, total (t)-tau, phosphorylated (p)-tau, and amyloid-β (Aβ)42 in healthy controls (n = 38) and subjects with a clinical, genetic, CSF biomarker-based, and/or neuropathological diagnosis of FTD (n = 141) or AD (n = 60). Sub-analyses were conducted in a proportion of subjects with definite and/or probable frontotemporal lobar degeneration with tau (FTLD-TAU) (n = 42) or TDP43 pathology (FTLD-TDP) (n = 36). Both FTD and AD groups showed significantly increased CSF NfL levels in comparison to controls (p < 0.001). CSF NfL levels were significantly higher in FTD patients than in AD (p < 0.001), reaching the highest values in amyotrophic lateral sclerosis associated with FTD. Patients with probable and definite FTLD-TDP had significantly higher NfL levels (p < 0.001) and lower p-tau/t-tau values (p < 0.001) in comparison with probable and definite FTLD-TAU cases. NfL showed good diagnostic accuracy in the distinction between FTD and controls (AUC 0.862±0.027) and yielded an accuracy (AUC 0.861±0.045) comparable to that of the p-tau/t-tau ratio (AUC 0.814±0.050), with 80.0% sensitivity and 81.0% specificity, in the discrimination between probable/definite FTLD-TAU and FTLD-TDP. Our data further validate CSF NfL as a surrogate biomarker of neurodegeneration and disease severity in patients with FTD spectrum. Moreover, they demonstrate a good diagnostic value for NfL and p-tau/t-tau ratio in the discrimination between FTLD-TAU and FTLD-TDP.

• Authors: Samir Abu-Rumeileh, Nicola Mometto, Anna Bartoletti-Stella, Barbara Polischi, Federico Oppi, Roberto Poda, Michelangelo Stanzani-Maserati, Pietro Cortelli, Rocco Liguori, Sabina Capellari, Piero Parchi
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 66 Issue 2 Pg. 551-563 ( 2018) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 30320576 (Publication Type: Journal Article)

Chemical References

• Amyloid beta-Peptides
• Biomarkers
• Neurofilament Proteins
• neurofilament protein L
• tau Proteins

Topics

• Aged
• Alzheimer Disease (cerebrospinal fluid, diagnostic imaging, genetics)
• Amyloid beta-Peptides (cerebrospinal fluid)
• Biomarkers (cerebrospinal fluid)
• Cohort Studies
• Female
• Frontotemporal Dementia (cerebrospinal fluid, diagnostic imaging, genetics)
• Humans
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Neurofilament Proteins (cerebrospinal fluid)
• Neuropsychological Tests
• ROC Curve
• Tomography Scanners, X-Ray Computed
• Verbal Learning (physiology)
• tau Proteins (cerebrospinal fluid)