title: No interaction between tau and TDP-43 pathologies in either frontotemporal lobar degeneration or motor neurone disease.
abstract: BACKGROUND
  Frontotemporal lobar degeneration (FTLD) is classified mainly into FTLD-tau and FTLD-TDP according to the protein present within inclusion bodies. While such a classification implies only a single type of protein should be present, recent studies have demonstrated dual tau and TDP-43 proteinopathy can occur, particularly in inherited FTLD.
  
  
  METHODS
  We therefore investigated 33 patients with FTLD-tau (including 9 with MAPT mutation) for TDP-43 pathological changes, and 45 patients with FTLD-TDP (including 12 with hexanucleotide expansion in C9ORF72 and 12 with GRN mutation), and 23 patients with motor neurone disease (3 with hexanucleotide expansion in C9ORF72), for tauopathy.
  
  
  RESULTS
  TDP-43 pathological changes, of the kind seen in many elderly individuals with Alzheimer's disease, were seen in only two FTLD-tau cases--a 70-year-old male with exon 10 + 13 mutation in MAPT, and a 73-year-old female with corticobasal degeneration. Such changes were considered to be secondary and probably reflective of advanced age. Conversely, there was generally only scant tau pathology, usually only within hippocampus and/or entorhinal cortex, in most patients with FTLD-TDP or MND. The extent of tau pathology in FTLD-TDP and MND, as with amyloid β protein, may relate to increased age and possession of Apolipoprotein ε4 allele.
  
  
  CONCLUSIONS
  We find no predilection or predisposition towards an accompanying TDP-43 pathology in patients with FTLD-tau, irrespective of presence or absence of MAPT mutation, or that genetic changes associated with FTLD-TDP predispose towards excessive tauopathy. Where the two processes coexist, this is limited and probably causatively independent of each other.
authors.affiliation: Clinical and Cognitive Sciences Research Group, Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Salford Royal Hospital, Salford.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Robinson
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Thompson
authors.forename: Lindsey
authors.initials: L
authors.lastname: Weedon
authors.forename: Sara
authors.initials: S
authors.lastname: Rollinson
authors.forename: Stuart
authors.initials: S
authors.lastname: Pickering-Brown
authors.forename: Julie S
authors.initials: JS
authors.lastname: Snowden
authors.forename: Yvonne S
authors.initials: YS
authors.lastname: Davidson
authors.forename: David M A
authors.initials: DM
authors.lastname: Mann
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000073885:C9orf72 Protein; D002540:Cerebral Cortex / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics*; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000235:genetics*; D000077153:Progranulins; D011506:Proteins / Q000235:genetics; D016875:tau Proteins / Q000235:genetics*
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D004268:DNA-Binding Proteins; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; C054369:MAPT protein, human; D000077153:Progranulins; D011506:Proteins; C000598624:TARDBP protein, human; D016875:tau Proteins
keywords: C9ORF72; TDP-43; progranulin gene; tau; tau gene