Cerebrospinal fluid (CSF) tau and amyloid beta42 (A beta 42) protein abnormalities correlate with executive dysfunction in myotonic dystrophy type 1 (DM1) and type 2 (DM2)

Objective: To correlate CSF tau (total, t-tau; phsophorylated, p-tau181) and A42 protein levels to neuropsychological profiles in DM1 and DM2. Background: Preliminary data in patients with DM1 suggest that the Tau pathology in these patients may be different from Alzheimers disease. Design/Methods: 33 patients with moderately severe DM1 (n = 23) and genetically-confirmed DM2 (n = 10) were subjected to neuromuscular and neuropsychological assessments. Results were compared to 16 age-, sex- and education-matched controls and to 29 frontotemporal (FTD) dementia patients. CSF t-tau, p-tau181 and A42 proteins were determined by using ELISA (Innogenetics, Belgium). Results: (i) CSF levels of t-tau and p-tau181 proteins were increased in more than 3/4 of patients with DM1(t-tau: 378.2 pg/ml 289.6; p-tau181:58.3 pg/ml 36.9) and in 1/2 of DM2 (t-tau:272.5 pg/ml 179.5; p-tau181: 42.5 pg/ml 19), DM1 t-tau and p-tau181significantly higher than controls (p<0.05) but t-tau lower in DM1 compared to FTD (431.2 pg/ml 33.8, p = 0.01) and p-tau181 similar between DM1 and FTD (48.7 pg/ml 4.9); (iii) A42 levels were not significantly different in DM1 (941.3 pg/ml 328.3), DM2 (798pg/ml 258.3) and controls (901.88 pg/ml 250.4) and were similar to FTD (694.3 55.2); (iv) T-tau and p-tau181 levels correlated with frontal lobe test functions (TEA, p>0,05); (v) Significant inverse correlations were found between age at onset and t-tau in DM2 (r=-0.673, p < 0.05). (v) No correlation was found between disease duration, muscle strength scores, muscle disability and CTG or CCTG repeat size in DM1 and DM2. Conclusions/Relevance: DM1 and DM2 are associated with a significant increase in CSF t- and p-tau levels along with normal A42 protein levels. The correlation to tests of frontal lobe function suggests these CSF biomarkers may play a role in the cognitive and behavioural profiles of DM1 and DM2. However, the usefulness for an attractive therapeutic target of cerebral involvement needs to be further addressed.