Elevated YKL-40 and low sAPP?:YKL-40 ratio in antemortem cerebrospinal fluid of patients with pathologically confirmed FTLD.

ABSTRACT: OBJECTIVES:The combination of high YKL-40 (a glial inflammatory marker) and low sAPP? (a soluble ? 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 sAPP? 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?, higher levels of YKL-40 and lower sAPP?: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?: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? and high YKL-40 in CSF is associated with FTLD. These biomarkers could be useful in particular clinical settings when FTLD is suspected.

SUBMITTER: Alcolea D 

PROVIDER: S-EPMC6351153 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature