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Histone deacetylases ( HDACs ) in frontotemporal lobar degeneration
Author(s) -
Whitehouse Amy,
Doherty Klara,
Yeh Hsin Hsien,
Robinson Andrew C.,
Rollinson Sara,
PickeringBrown Stuart,
Snowden Julie,
Thompson Jennifer C,
Davidson Yvonne S.,
Mann David M. A.
Publication year - 2015
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/nan.12153
Subject(s) - frontotemporal lobar degeneration , c9orf72 , pathogenesis , immunostaining , biology , pathology , dentate gyrus , neuroscience , frontotemporal dementia , hdac4 , histone , hippocampus , medicine , immunohistochemistry , dementia , genetics , histone deacetylase , disease , gene
Aims 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‐ P icks 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 P ick bodies.