PT  - JOURNAL ARTICLE
AU  - Daniel Alcolea
AU  - David J Irwin
AU  - Ignacio Illán-Gala
AU  - Laia Muñoz
AU  - Jordi Clarimón
AU  - Corey T McMillan
AU  - Juan Fortea
AU  - Rafael Blesa
AU  - Edward B Lee
AU  - John Q Trojanowski
AU  - Murray Grossman
AU  - Alberto Lleó
TI  - Elevated YKL-40 and low sAPPβ:YKL-40 ratio in antemortem cerebrospinal fluid of patients with pathologically confirmed FTLD
AID  - 10.1136/jnnp-2018-318993
DP  - 2019 Feb 01
TA  - Journal of Neurology, Neurosurgery & Psychiatry
PG  - 180--186
VI  - 90
IP  - 2
4099  - http://jnnp.bmj.com/content/90/2/180.short
4100  - http://jnnp.bmj.com/content/90/2/180.full
SO  - J Neurol Neurosurg Psychiatry2019 Feb 01; 90
AB  - Objectives The combination of high YKL-40 (a glial inflammatory marker) and low sAPPβ (a soluble β 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 CSF 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 sAPPβ 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 sAPPβ, higher levels of YKL-40 and lower sAPPβ: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 sAPPβ: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 sAPPβ and high YKL-40 in CSF is associated with FTLD. These biomarkers could be useful in particular clinical settings when FTLD is suspected.