title: Cerebrospinal fluid biomarkers for Alzheimer's disease in patients with frontotemporal lobar degeneration and amyotrophic lateral sclerosis with the C9ORF72 repeat expansion.
abstract: BACKGROUND
  The C9ORF72 expansion is one of the most common causes of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). The C9ORF72 expansion is associated with TDP-43 and p62 neuropathology, and amyloid plaques and neurofibrillary tangles are not common in patients with the C9ORF72 expansion. Therefore, we hypothesized that cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease [AD; Aβ1-42, total tau (T-tau) and phospho-tau] are normal in these patients.
  
  
  METHODS
  The CSF Aβ1-42, T-tau and phospho-tau levels were measured in 40 Finnish patients with the C9ORF72 expansion (29 FTLD, 10 ALS and 1 FTLD-ALS) using ELISA.
  
  
  RESULTS
  A decreased Aβ1-42 level was found in 25% of cases, while there were only single cases with changes in the t-Tau or phospho-tau level. The patients with abnormal biomarkers fulfilled the clinical criteria of the behavioral variant frontotemporal dementia and expressed no clinical signs of AD.
  
  
  CONCLUSIONS
  In clinical diagnostics, a decreased CSF Aβ1-42 level does not exclude the C9ORF72 expansion associated with FTLD.
authors: Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland.
authors: Anna
authors: A
authors: Kämäläinen
authors: Sanna-Kaisa
authors: SK
authors: Herukka
authors: Päivi
authors: P
authors: Hartikainen
authors: Seppo
authors: S
authors: Helisalmi
authors: Virpi
authors: V
authors: Moilanen
authors: Anna
authors: A
authors: Knuuttila
authors: Lilja
authors: L
authors: Jansson
authors: Pentti J
authors: PJ
authors: Tienari
authors: Anne M
authors: AM
authors: Remes
mesh_terms: D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology; D000073885:C9orf72 Protein; D015331:Cohort Studies; D042622:DNA Repeat Expansion; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000134:cerebrospinal fluid* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics
chemical_list: D015415:Biomarkers; D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D004268:DNA-Binding Proteins; D011506:Proteins; D016875:tau Proteins