Diagnostic value of cerebrospinal fluid tau, neurofilament, and progranulin in definite frontotemporal lobar degeneration

作者：Goossens Joery; Bjerke Maria; Van Mossevelde Sara; Van den Bossche Tobi; Goeman Johan; De Vil Bart; Sieben Anne; Martin Jean Jacques; Cras Patrick; De Deyn Peter Paul; Van Broeckhoven Christine; Van der Zee Julie; Engelborghs Sebastiaan^*

来源：Alzheimer's Research and Therapy, 2018, 10(1): 31.

DOI：10.1186/s13195-018-0364-0

• Frontotemporal lobar degeneration
• Alzheimer's disease
• Cerebrospinal fluid
• Biomarkers
• Differential diagnosis
• Tau
• Neurofilament
• Progranulin

Background: We explored the diagnostic performance of cerebrospinal fluid (CSF) biomarkers in allowing differentiation between frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD), as well as between FTLD pathological subtypes.
Methods: CSF levels of routine AD biomarkers (phosphorylated tau (p-tau(181)), total tau (t-tau), and amyloid-beta (A beta)(1-42)) and neurofilament proteins, as well as progranulin levels in both CSF and serum were quantified in definite FTLD (n = 46), clinical AD (n = 45), and cognitively healthy controls (n = 20). FTLD subgroups were defined by genetic carrier status and/or postmortem neuropathological confirmation (FTLD-TDP: n = 34, including FTLD-C9orf72: n = 19 and FTLD-GRN: n = 9; FTLD-tau: n = 10).
Results: GRN mutation carriers had significantly lower progranulin levels compared to other FTLD patients, AD, and controls. Both t-tau and p-tau181 were normal in FTLD patients, even in FTLD-tau. A beta(1-42) levels were very variable in FTLD. Neurofilament light chain (Nf-L) was significantly higher in FTLD compared with AD and controls. The reference logistic regression model based on the established AD biomarkers could be improved by the inclusion of CSF Nf-L, which was also important for the differentiation between FTLD and controls. Within the FTLD cohort, no significant differences were found between FTLD-TDP and FTLD-tau, but GRN mutation carriers had higher t-tau and Nf-L levels than C9orf72 mutation carriers and FTLD-tau patients.
Conclusions: There is an added value for Nf-L in the differential diagnosis of FTLD. Progranulin levels in CSF depend on mutation status, and GRN mutation carriers seem to be affected by more severe neurodegeneration.

• 出版日期2018-3-20