Cerebrospinal fluid biomarkers of neurodegeneration in patients with juvenile and classic myotonic dystrophy type 1

Background and purposeThe aim of the present study was to analyze cerebrospinal fluid (CSF) levels of total tau (T-tau), phosphorylated tau (P-tau) and the 42-amino-acid form of -amyloid (A(42)) in patients with myotonic dystrophy type 1 (DM1), and their possible correlations with cognitive and behavioral manifestations in these patients. MethodsLumbar puncture was performed in 74 patients with DM1 [27 with the childhood/juvenile form (jDM1) and 47 with the adult form (aDM1) of the disease] and 26 control subjects who were subjected to orthopedic surgery. Sandwich ELISA was used for measuring the levels of T-tau, P-tau and A(42). ResultsThe CSF level of A(42) was at its lowest in patients with jDM1 and at its highest in controls (P<0.05). A tendency of T-tau and P-tau to increase was greater in aDM1 patients than in jDM1 patients and controls (P>0.05). In both jDM1 and aDM1 patients, significant correlations were found between A(42) and T-tau (rho=0.81 and rho=0.67, respectively, P<0.01), as well as between A(42) and P-tau (rho=0.87 and rho=0.67, respectively, P<0.01). The A(42)/P-tau ratio decreased with age in aDM1 patients (rho=-0.30, P<0.05). Only the level of A(42) in the CSF of jDM1 patients was correlated with the size of the CTG expansion (rho=-0.53, P<0.05). Only a few correlations were observed between levels of biomarkers and neuropsychological testing. ConclusionThe CSF level of A(42) was decreased in patients with jDM1, whilst the A(42)/P-tau ratio was decreased in aDM1 patients. Positive correlations between A(42), T-tau and P-tau were observed in both forms of disease. Further studies with larger cohorts of DM1 patients are necessary. Click here to view the accompanying paper in this issue.