Neuropathological background of phenotypical variability in frontotemporal dementia

Keith Anthony Josephs, John R. Hodges, Julie S. Snowden, Ian R. MacKenzie, Manuela Neumann, David M. Mann, Dennis W Dickson

Research output: Contribution to journalArticle

232 Citations (Scopus)

Abstract

Frontotemporal lobar degeneration (FTLD) is the umbrella term encompassing a heterogeneous group of pathological disorders. With recent discoveries, the FTLDs have been show to classify nicely into three main groups based on the major protein deposited in the brain: FTLD-tau, FTLD-TDP and FTLD-FUS. These pathological groups, and their specific pathologies, underlie a number of well-defined clinical syndromes, including three frontotemporal dementia (FTD) variants [behavioral variant frontotemporal dementia (bvFTD), progressive non-fluent aphasia, and semantic dementia (SD)], progressive supranuclear palsy syndrome (PSPS) and corticobasal syndrome (CBS). Understanding the neuropathological background of the phenotypic variability in FTD, PSPS and CBS requires large clinicopathological studies. We review current knowledge on the relationship between the FTLD pathologies and clinical syndromes, and pool data from a number of large clinicopathological studies that collectively provide data on 544 cases. Strong relationships were identified as follows: FTD with motor neuron disease and FTLD-TDP; SD and FTLD-TDP; PSPS and FTLD-tau; and CBS and FTLD-tau. However, the relationship between some of these clinical diagnoses and specific pathologies is not so clear cut. In addition, the clinical diagnosis of bvFTD does not have a strong relationship to any FTLD subtype or specific pathology and therefore remains a diagnostic challenge. Some evidence suggests improved clinicopathological association of bvFTD by further refining clinical characteristics. Unlike FTLD-tau and FTLD-TDP, FTLD-FUS has been less well characterized, with only 69 cases reported. However, there appears to be some associations between clinical phenotypes and FTLD-FUS pathologies. Clinical diagnosis is therefore promising in predicting molecular pathology.

Original languageEnglish (US)
Pages (from-to)137-153
Number of pages17
JournalActa Neuropathologica
Volume122
Issue number2
DOIs
StatePublished - Aug 2011

Fingerprint

Frontotemporal Lobar Degeneration
Frontotemporal Dementia
Progressive Supranuclear Palsy
Pathology
Clinical Pathology
Molecular Pathology
Aphasia

Keywords

  • Frontotemporal lobar degeneration
  • FUS
  • Progressive supranuclear palsy
  • Tau
  • TDP-43

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Cellular and Molecular Neuroscience

Cite this

Neuropathological background of phenotypical variability in frontotemporal dementia. / Josephs, Keith Anthony; Hodges, John R.; Snowden, Julie S.; MacKenzie, Ian R.; Neumann, Manuela; Mann, David M.; Dickson, Dennis W.

In: Acta Neuropathologica, Vol. 122, No. 2, 08.2011, p. 137-153.

Research output: Contribution to journalArticle

Josephs, Keith Anthony ; Hodges, John R. ; Snowden, Julie S. ; MacKenzie, Ian R. ; Neumann, Manuela ; Mann, David M. ; Dickson, Dennis W. / Neuropathological background of phenotypical variability in frontotemporal dementia. In: Acta Neuropathologica. 2011 ; Vol. 122, No. 2. pp. 137-153.
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