CSF biomarkers in frontotemporal lobar degeneration with known pathology

Abstract

Objective: To evaluate the diagnostic value of CSF biomarkers in patients with known pathology due to frontotemporal lobar degeneration (FTLD).

Background: It is important to distinguish FTLD from other neurodegenerative diseases like Alzheimer disease (AD), but this may be difficult clinically because of atypical presentations.

Methods: Patients with FTLD (n = 30) and AD (n = 19) were identified at autopsy or on the basis of genetic testing at University of Pennsylvania and Erasmus University Medical Center. CSF was obtained during a diagnostic lumbar puncture and was analyzed using assays for total tau and amyloid-beta 1-42 (A beta(42)). Patients also were assessed with a brief neuropsychological battery.

Results: CSF total tau level and the ratio of CSF total tau to A beta(42) (tau/A beta(42)) were significantly lower in FTLD than in AD. Receiver operating characteristic curve analyses confirmed that the CSF tau/A beta(42) ratio is sensitive and specific at discriminating between FTLD and AD, and is more successful at this than CSF total tau alone. Although some neuropsychological measures are significantly different in autopsy-proven FTLD and AD, combining these neuropsychological measures with CSF biomarkers did not improve the ability to distinguish FTLD from AD.

Conclusions: The ratio of CSF tau/A beta(42) is a sensitive and specific biomarker at discriminating frontotemporal lobar degeneration from Alzheimer disease in patients with known pathology.

Figure 1

CSF total tau, Aβ₄₂, and tau/Aβ₄₂ ratio in frontotemporal lobar degeneration (FTLD), Alzheimer disease (AD), and control groups

Figure 2

Scatterplot and receiver operating characteristic curves of CSF tau, Aβ₄₂, and tau/Aβ₄₂ ratio in patients with frontotemporal lobar degeneration (FTLD) and Alzheimer disease (AD) (A) Scatterplot of CSF tau and Aβ₄₂ levels in patients with FTLD and AD. (B) Receiver operating characteristic curves of CSF tau, Aβ₄₂, and tau/Aβ₄₂ ratio in patients with FTLD and AD. Using the raw data depicted in the figure, the CSF tau/Aβ₄₂ ratio at a cutoff of 1.06 has sensitivity = 78.9%, specificity = 96.6%, positive predictive value = 93.75%, and positive likelihood ratio = 23.21 to distinguish between FTLD and AD. CSF tau, at a cutoff of 403.05 pg/mL, has sensitivity = 68.4%, specificity = 89.7%, positive predictive value = 81.25%, and positive likelihood ratio = 6.64 to distinguish between FTLD and AD.