Elevated YKL-40 and low sAPP beta: YKL-40 ratio in antemortem cerebrospinal fluid of patients with pathologically confirmed FTLD
Por:
Alcolea, D, Irwin, DJ, Illan-Gala, I, Munoz, L, Clarimon, J, McMillan, CT, Fortea, J, Blesa, R, Lee, EB, Trojanowski, JQ, Grossman, M, Lleo, A
Publicada:
1 feb 2019
Resumen:
Objectives The combination of high YKL-40 (a glial inflammatory marker) and low sAPP beta (a soluble beta fragment of amyloid precursor protein) in cerebrospinal fluid (CSF) has been associated with frontotemporal lobar degeneration (FTLD) in clinical series. We investigate these biomarkers in a neuropathologically confirmed cohort of patients with FTLD.
Methods CS F samples were selected from the Penn FTD Center (University of Pennsylvania). Participants were followed to autopsy and had a neuropathological diagnosis of FTLD-Tau (n= 24), transactive response DNA-binding protein with 43 kDa (FTLD-TDP) (n= 25) or Alzheimer's disease (AD, n= 97). We compared levels of YKL-40 and sAPP beta between groups and with cognitively normal controls (n= 77), and assessed their diagnostic utility using receiver operating characteristic curves. We also investigated the effect of AD copathology and the correlation between these CSF markers and tau burden at autopsy.
Results Both FTLD groups had lower levels of sAPP beta, higher levels of YKL-40 and lower sAPP beta: YKL-40 ratio in CSF compared with controls. The group of pure FTLD-Tau (without AD copathology) showed higher levels of YKL-40 than AD and than pure FTLD-TDP. YKL-40 levels correlated with pathological tau burden. The sAPP beta: YKL-40 ratio had an area under the curve (AUC) of 0.91 (95% CI 0.86 to 0.96) to distinguish subjects with FTLD from controls, but lower values to distinguish FTLD from AD (AUC 0.70; 95% CI 0.61 to 0.79) and to discriminate FTLD-Tau from FTLD-TDP (AUC 0.67; 95% CI 0.51 to 0.82).
Conclusions Our study provides pathological confirmation that the combination of low sAPP beta and high YKL-40 in CSF is associated with FTLD. These biomarkers could be useful in particular clinical settings when FTLD is suspected.
Filiaciones:
Alcolea, D:
Univ Autonoma Barcelona, St Pau Memory Unit, Dept Neurol, Inst Invest Biomed St Pau,Hosp St Pau, Barcelona, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Irwin, DJ:
Univ Penn, Penn FTD Ctr, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA
Illan-Gala, I:
Univ Autonoma Barcelona, St Pau Memory Unit, Dept Neurol, Inst Invest Biomed St Pau,Hosp St Pau, Barcelona, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Munoz, L:
Univ Autonoma Barcelona, St Pau Memory Unit, Dept Neurol, Inst Invest Biomed St Pau,Hosp St Pau, Barcelona, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Clarimon, J:
Univ Autonoma Barcelona, St Pau Memory Unit, Dept Neurol, Inst Invest Biomed St Pau,Hosp St Pau, Barcelona, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
McMillan, CT:
Univ Penn, Penn FTD Ctr, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA
Fortea, J:
Univ Autonoma Barcelona, St Pau Memory Unit, Dept Neurol, Inst Invest Biomed St Pau,Hosp St Pau, Barcelona, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Blesa, R:
Univ Autonoma Barcelona, St Pau Memory Unit, Dept Neurol, Inst Invest Biomed St Pau,Hosp St Pau, Barcelona, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Lee, EB:
Univ Penn, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA
Trojanowski, JQ:
Univ Penn, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA
Grossman, M:
Univ Penn, Penn FTD Ctr, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA
Lleo, A:
Univ Autonoma Barcelona, St Pau Memory Unit, Dept Neurol, Inst Invest Biomed St Pau,Hosp St Pau, Barcelona, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Green Accepted
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