CSF sAPP beta, YKL-40, and NfL along the ALS-FTD spectrum
Por:
Illan-Gala, I, Alcolea, D, Montal, V, Dols-Icardo, O, Munoz, L, de Luna, N, Turon-Sans, J, Cortes-Vicente, E, Sanchez-Saudinos, MB, Subirana, A, Sala, I, Blesa, R, Clarimon, J, Fortea, J, Rojas-Garcia, R, Lleo, A
Publicada:
23 oct 2018
Resumen:
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.
Filiaciones:
Illan-Gala, I:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Alcolea, D:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Montal, V:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Dols-Icardo, O:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Munoz, L:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
de Luna, N:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, Neuromuscular Dis Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Turon-Sans, J:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, Neuromuscular Dis Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Cortes-Vicente, E:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, Neuromuscular Dis Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Sanchez-Saudinos, MB:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Subirana, A:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Sala, I:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Blesa, R:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Clarimon, J:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Fortea, J:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Rojas-Garcia, R:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, Neuromuscular Dis Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Lleo, A:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
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