Neuropathological background of phenotypical variability in frontotemporal dementia

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....

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Main Authors:	Josephs, Keith A., Hodges, John R., Snowden, Julie S., Mackenzie, Ian R., Neumann, Manuela, Mann, David M., Dickson, Dennis W.
Format:	Online
Language:	English
Published:	Springer-Verlag 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232515/

id	pubmed-3232515
recordtype	oai_dc
spelling	pubmed-32325152011-12-27 Neuropathological background of phenotypical variability in frontotemporal dementia Josephs, Keith A. Hodges, John R. Snowden, Julie S. Mackenzie, Ian R. Neumann, Manuela Mann, David M. Dickson, Dennis W. Review 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. Springer-Verlag 2011-05-26 2011-08 /pmc/articles/PMC3232515/ /pubmed/21614463 http://dx.doi.org/10.1007/s00401-011-0839-6 Text en © The Author(s) 2011
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Josephs, Keith A. Hodges, John R. Snowden, Julie S. Mackenzie, Ian R. Neumann, Manuela Mann, David M. Dickson, Dennis W.
spellingShingle	Josephs, Keith A. 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
author_facet	Josephs, Keith A. Hodges, John R. Snowden, Julie S. Mackenzie, Ian R. Neumann, Manuela Mann, David M. Dickson, Dennis W.
author_sort	Josephs, Keith A.
title	Neuropathological background of phenotypical variability in frontotemporal dementia
title_short	Neuropathological background of phenotypical variability in frontotemporal dementia
title_full	Neuropathological background of phenotypical variability in frontotemporal dementia
title_fullStr	Neuropathological background of phenotypical variability in frontotemporal dementia
title_full_unstemmed	Neuropathological background of phenotypical variability in frontotemporal dementia
title_sort	neuropathological background of phenotypical variability in frontotemporal dementia
description	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.
publisher	Springer-Verlag
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232515/
_version_	1611492571368914944

Neuropathological background of phenotypical variability in frontotemporal dementia

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