• Ignacio Illán-Gala, Daniel Alcolea, Victor Montal, Oriol Dols-Icardo, Laia Muñoz, Noemi de Luna, Janina Turón-Sans, Elena Cortés-Vicente, Ma Belén Sánchez-Saudinós, Andrea Subirana, Isabel Sala, Rafael Blesa, Jordi Clarimón, Juan Fortea, Ricard Rojas-García, and Alberto Lleó.
• From the Sant Pau Memory Unit, Department of Neurology, Biomedical Research Institute Sant Pau (I.I.-G., D.A., V.M., O.D.-I., L.M., M.B.S.-S., A.S., I.S., R.B., J.C., J.F., A.L.), and Neuromuscular Diseases Unit, Department of Neurology (N.d.L., J.T.-S., E.C.-V., R.R.-G.), Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED) (I.I.-G., D.A., V.M., O.D.-I., R.B., J.C., J.F., A.L.); and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) (N.d.L., J.T.-S., E.C.-V., R.R.-G.), Madrid, Spain.
• Neurology. 2018 Oct 23; 91 (17): e1619-e1628.

ObjectiveTo investigate the clinical utility of 3 CSF biomarkers along the clinical spectrum of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).MethodsWe analyzed 3 CSF biomarkers: the soluble β-fragment of amyloid precursor protein (sAPPβ), 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.ResultsWe found increased levels of YKL-40 and decreased levels of sAPPβ in both FTD and ALS groups compared to controls. The lowest sAPPβ levels and sAPPβ/YKL-40 ratio were found in the FTD group. In FTD, sAPPβ and the sAPPβ/YKL-40 ratio correlated with the disease severity. In the whole ALS-FTD spectrum, NfL levels and the NfL:sAPPβ 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 sAPPβ/YKL-40 ratio showed a positive correlation with cortical thickness in frontotemporal regions.ConclusionssAPPβ, YKL-40, and NfL could represent valuable tools for the staging and prognosis of patients within the ALS-FTD clinical spectrum.Classification Of EvidenceThis study provides Class III evidence that CSF levels of sAPPβ, YKL-40, and NfL are useful to assess frontotemporal neurodegeneration and the progression rate in the ALS-FTD continuum.© 2018 American Academy of Neurology.

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