title: TDP-43 plasma levels are higher in amyotrophic lateral sclerosis.
abstract: Our objective was to investigate TDP-43 plasma levels in patients with amyotrophic lateral sclerosis (ALS). TDP-43 has been identified as a major component of protein inclusions in the brain of patients with ALS; mutations in the corresponding gene (TARDBP) have also been identified. Although increased TDP-43 levels have been reported in the cerebrospinal fluid, plasma levels have not yet been assessed in patients with ALS. TDP-43 levels were quantified by sandwich ELISA in plasma of 219 patients and 100 controls. In addition, we sequenced exon 6 of TARDBP, and performed longitudinal TDP-43 plasma measurements in a subset of patients. Results showed that TDP-43 plasma levels were significantly increased in patients with ALS (p=0.023) and we found a positive correlation with age in patients and controls. Longitudinal measurements of TDP-43 plasma levels showed an increase in only one patient, with stable levels in five others. Three TARDBP variations were identified in the ALS group (1.7%), but the association with TDP-43 plasma levels was ambiguous. In conclusion, our data indicate that TDP-43 plasma levels may have potential as a marker for ALS. A genotype-phenotype relationship could not, however, be established in this cohort.
authors.affiliation: Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Verstraete
authors.forename: H Bea
authors.initials: HB
authors.lastname: Kuiperij
authors.forename: Marka M
authors.initials: MM
authors.lastname: van Blitterswijk
authors.forename: Jan H
authors.initials: JH
authors.lastname: Veldink
authors.forename: H Jurgen
authors.initials: HJ
authors.lastname: Schelhaas
authors.forename: Leonard H
authors.initials: LH
authors.lastname: van den Berg
authors.forename: Marcel M
authors.initials: MM
authors.lastname: Verbeek
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000097:blood* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins