Cerebrospinal Fluid TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis Patients with and without the C9ORF72 Hexanucleotide Expansion

<b><i>Background:</i></b> TDP-43 is the main protein component of ubiquitinated inclusions in a subgroup of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) patients. The <i>C9ORF72</i> hexanucleotide expansion is one of the main mutations associated with TDP-43 pathology in FTLD and ALS. Our aim was to analyze cerebrospinal fluid (CSF) TDP-43 levels and Alzheimer's disease biomarkers in FTLD and ALS patients and to test whether the <i>C9ORF72</i> expansion carrier status affects these variables. <b><i>Methods:</i></b> The patient cohort consisted of 90 clinically well-characterized FTLD (n = 69) and ALS (n = 21) patients. There were 30 patients with the <i>C9ORF72</i> expansion and 60 patients without the expansion. CSF TDP-43, Aβ_1-42, t-tau, and phospho-tau levels were measured using commercial ELISA kits. <b><i>Results:</i></b> There was no difference in CSF TDP-43 levels between the <i>C9ORF72</i> expansion carriers and the noncarriers. CSF TDP-43 levels were higher in ALS patients than in FTLD patients, and this finding was independent of the <i>C9ORF72</i> expansion carrier status. Males had significantly higher TDP-43 levels than females (p = 0.008 in the total cohort). <b><i>Conclusion:</i></b> CSF TDP-43 does not seem to distinguish the <i>C9ORF72</i> expansion carriers from noncarriers. However, higher CSF TDP-43 levels were detected in ALS than in FTLD, which might be an indicator of a more rapid progression of TDP-43 pathology in ALS.