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A reassessment of the neuropathology of frontotemporal dementia linked to chromosome 3

Holm, Ida Elisabeth; Englund, Elisabet LU ; Mackenzie, Ian R. A.; Johannsen, Peter and Isaacs, Adrian M. (2007) In Journal of Neuropathology and Experimental Neurology 66(10). p.884-891
Abstract
A large Danish family has previously been reported in which autosomal dominant frontotemporal dementia (FTD) is genetically linked to chromosome 3 (FTD-3). A mutation was recently identified in the CHMP2B gene that is probably responsible for causing disease in this family. Because of its neuropathologic findings, FTD-3 was originally categorized as a subtype of frontotemporal lobar degeneration, termed "dementia lacking distinctive histopathology." We now report a reevaluation of the neuropathologic changes in this family. Postmortem material from 4 affected family members was available for examination. Gross examination revealed generalized cortical atrophy that was most severe in frontal and temporal cortices. Microscopy showed loss of... (More)
A large Danish family has previously been reported in which autosomal dominant frontotemporal dementia (FTD) is genetically linked to chromosome 3 (FTD-3). A mutation was recently identified in the CHMP2B gene that is probably responsible for causing disease in this family. Because of its neuropathologic findings, FTD-3 was originally categorized as a subtype of frontotemporal lobar degeneration, termed "dementia lacking distinctive histopathology." We now report a reevaluation of the neuropathologic changes in this family. Postmortem material from 4 affected family members was available for examination. Gross examination revealed generalized cortical atrophy that was most severe in frontal and temporal cortices. Microscopy showed loss of cortical neurons. microvacuolation of layer 11, mild gliosis, and demyelination of the deep white matter. Results of immunohistochemical staining for alpha-synuclein, prion protein, neurofilament, and tau protein were unremarkable. Variable numbers of small, round, ubiquitin-positive cytoplasmic inclusions were present in the dentate granule layer of the hippocampus in all 4 cases. Rare ubiquitin-positive inclusions were also found in frontal and temporal cortical neurons. These inclusions were also positive for p62 but not for TDP-43. The finding of ubiquitin- and p62-positive, TDP-43-neaative cytoplasmic inclusions in the hippocampus and neocortex suggests reclassification of the neuropathology of FTD-3 as a unique subtype of frontotemporal lobar degeneration with ubiquitin-positive inclusions that are TDP-43 -negative. (Less)
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organization
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Contribution to journal
publication status
published
subject
keywords
frontotemporal lobar degeneration, chromosome 3, dementia lacking distinctive histopathology, ubiquitin
in
Journal of Neuropathology and Experimental Neurology
volume
66
issue
10
pages
884 - 891
publisher
American Association of Neuropathologists
external identifiers
  • wos:000250159200002
  • scopus:34948838317
ISSN
1554-6578
language
English
LU publication?
yes
id
aecfe43e-a0ee-4d59-8f48-8e6ebd8ee1ae (old id 655177)
alternative location
http://www.jneuropath.com/pt/re/jnen/abstract.00005072-200710000-00002.htm
date added to LUP
2007-12-12 14:45:51
date last changed
2017-11-12 03:59:04
@article{aecfe43e-a0ee-4d59-8f48-8e6ebd8ee1ae,
  abstract     = {A large Danish family has previously been reported in which autosomal dominant frontotemporal dementia (FTD) is genetically linked to chromosome 3 (FTD-3). A mutation was recently identified in the CHMP2B gene that is probably responsible for causing disease in this family. Because of its neuropathologic findings, FTD-3 was originally categorized as a subtype of frontotemporal lobar degeneration, termed "dementia lacking distinctive histopathology." We now report a reevaluation of the neuropathologic changes in this family. Postmortem material from 4 affected family members was available for examination. Gross examination revealed generalized cortical atrophy that was most severe in frontal and temporal cortices. Microscopy showed loss of cortical neurons. microvacuolation of layer 11, mild gliosis, and demyelination of the deep white matter. Results of immunohistochemical staining for alpha-synuclein, prion protein, neurofilament, and tau protein were unremarkable. Variable numbers of small, round, ubiquitin-positive cytoplasmic inclusions were present in the dentate granule layer of the hippocampus in all 4 cases. Rare ubiquitin-positive inclusions were also found in frontal and temporal cortical neurons. These inclusions were also positive for p62 but not for TDP-43. The finding of ubiquitin- and p62-positive, TDP-43-neaative cytoplasmic inclusions in the hippocampus and neocortex suggests reclassification of the neuropathology of FTD-3 as a unique subtype of frontotemporal lobar degeneration with ubiquitin-positive inclusions that are TDP-43 -negative.},
  author       = {Holm, Ida Elisabeth and Englund, Elisabet and Mackenzie, Ian R. A. and Johannsen, Peter and Isaacs, Adrian M.},
  issn         = {1554-6578},
  keyword      = {frontotemporal lobar degeneration,chromosome 3,dementia lacking distinctive histopathology,ubiquitin},
  language     = {eng},
  number       = {10},
  pages        = {884--891},
  publisher    = {American Association of Neuropathologists},
  series       = {Journal of Neuropathology and Experimental Neurology},
  title        = {A reassessment of the neuropathology of frontotemporal dementia linked to chromosome 3},
  volume       = {66},
  year         = {2007},
}