title: Histone deacetylases (HDACs) in frontotemporal lobar degeneration.
abstract: OBJECTIVE
  Frontotemporal lobar degeneration (FTLD) is clinically and pathologically heterogeneous. Although associated with variations in MAPT, GRN and C9ORF72, the pathogenesis of these, and of other nongenetic, forms of FTLD, remains unknown. Epigenetic factors such as histone regulation by histone deacetylases (HDAC) may play a role in the dysregulation of transcriptional activity, thought to underpin the neurodegenerative process.
  
  
  METHODS
  The distribution and intensity of HDACs 4, 5 and 6 was assessed semi-quantitatively in immunostained sections of temporal cortex with hippocampus, and cerebellum, from 33 pathologically confirmed cases of FTLD and 27 controls.
  
  
  RESULTS
  We found a significantly greater intensity of cytoplasmic immunostaining for HDAC4 and HDAC6 in granule cells of the dentate gyrus in cases of FTLD overall compared with controls, and specifically in cases of FTLD tau-Picks compared with FTLD tau-MAPT and controls. No differences were noted between FTLD-TDP subtypes, or between the different genetic and nongenetic forms of FTLD. No changes were seen in HDAC5 in any FTLD or control cases.
  
  
  CONCLUSIONS
  Dysregulation of HDAC4 and/or HDAC6 could play a role in the pathogenesis of FTLD-tau associated with Pick bodies, although their lack of immunostaining implies that such changes do not contribute directly to the formation of Pick bodies.
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, UK.
authors.forename: Amy
authors.initials: A
authors.lastname: Whitehouse
authors.forename: Klara
authors.initials: K
authors.lastname: Doherty
authors.forename: Hsin Hsien
authors.initials: HH
authors.lastname: Yeh
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Robinson
authors.forename: Sara
authors.initials: S
authors.lastname: Rollinson
authors.forename: Stuart
authors.initials: S
authors.lastname: Pickering-Brown
authors.forename: Julie
authors.initials: J
authors.lastname: Snowden
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Thompson
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; D018891:Dentate Gyrus / Q000473:pathology*; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000201:enzymology* / Q000473:pathology*; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000032:analysis / Q000096:biosynthesis*; D049669:History, 16th Century; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012097:Repressor Proteins / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D012097:Repressor Proteins; C400300:HDAC4 protein, human; C404500:HDAC5 protein, human; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases
keywords: frontotemporal lobar degeneration; histone deacetylases; immunohistochemistry