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Objective: To investigate the clinical utility of 3 CSF biomarkers along the clinical spectrum of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

Methods: We analyzed 3 CSF biomarkers: the soluble [beta]-fragment of amyloid precursor protein (sAPP[beta]), YKL-40, and neurofilament light (NfL) in FTD (n = 86), ALS (n = 38), and a group of age-matched cognitively normal controls (n = 49). Participants with FTD with a CSF profile of Alzheimer disease were excluded. We compared cross-sectional biomarker levels between groups, studied their correlation with cognitive and functional scales (global cognitive z score, frontotemporal lobar degeneration Clinical Dementia Rating, revised ALS Functional Rating Scale, and ALS progression rate), survival, and cortical thickness.

Results: We found increased levels of YKL-40 and decreased levels of sAPP[beta] in both FTD and ALS groups compared to controls. The lowest sAPP[beta] levels and sAPP[beta]/YKL-40 ratio were found in the FTD group. In FTD, sAPP[beta] and the sAPP[beta]/YKL-40 ratio correlated with the disease severity. In the whole ALS-FTD spectrum, NfL levels and the NfL:sAPP[beta] ratio correlated with global cognitive performance (r = -0.41, p < 0.001 and r = -0.44, p < 0.001, respectively). In the ALS group, YKL-40 correlated with disease progression rate (r = 0.51, p = 0.001) and was independently associated with shorter survival. In both FTD and ALS groups, the sAPP[beta]/YKL-40 ratio showed a positive correlation with cortical thickness in frontotemporal regions.

Conclusions: sAPP[beta], YKL-40, and NfL could represent valuable tools for the staging and prognosis of patients within the ALS-FTD clinical spectrum.

Classification of evidence: This study provides Class III evidence that CSF levels of sAPP[beta], YKL-40, and NfL are useful to assess frontotemporal neurodegeneration and the progression rate in the ALS-FTD continuum.

(C) 2018 American Academy of Neurology