Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration |
| |
Authors: | Nigel J Cairns Eileen H Bigio Ian R A Mackenzie Manuela Neumann Virginia M-Y Lee Kimmo J Hatanpaa Charles L White III Julie A Schneider Lea Tenenholz Grinberg Glenda Halliday Charles Duyckaerts James S Lowe Ida E Holm Markus Tolnay Koichi Okamoto Hideaki Yokoo Shigeo Murayama John Woulfe David G Munoz Dennis W Dickson Paul G Ince John Q Trojanowski David M A Mann |
| |
Institution: | Department of Neurology, Washington University School of Medicine, Campus Box 8118, 660 South Euclid Avenue, St Louis, MO, 63110, USA. |
| |
Abstract: | The aim of this study was to improve the neuropathologic recognition and provide criteria for the pathological diagnosis in
the neurodegenerative diseases grouped as frontotemporal lobar degeneration (FTLD); revised criteria are proposed. Recent
advances in molecular genetics, biochemistry, and neuropathology of FTLD prompted the Midwest Consortium for Frontotemporal
Lobar Degeneration and experts at other centers to review and revise the existing neuropathologic diagnostic criteria for
FTLD. The proposed criteria for FTLD are based on existing criteria, which include the tauopathies FTLD with Pick bodies,
corticobasal degeneration, progressive supranuclear palsy, sporadic multiple system tauopathy with dementia, argyrophilic
grain disease, neurofibrillary tangle dementia, and FTD with microtubule-associated tau (MAPT) gene mutation, also called FTD with parkinsonism linked to chromosome 17 (FTDP-17)]. The proposed criteria take into account
new disease entities and include the novel molecular pathology, TDP-43 proteinopathy, now recognized to be the most frequent
histological finding in FTLD. TDP-43 is a major component of the pathologic inclusions of most sporadic and familial cases
of FTLD with ubiquitin-positive, tau-negative inclusions (FTLD-U) with or without motor neuron disease (MND). Molecular genetic
studies of familial cases of FTLD-U have shown that mutations in the progranulin (PGRN) gene are a major genetic cause of FTLD-U. Mutations in valosin-containing protein (VCP) gene are present in rare familial forms of FTD, and some families with FTD and/or MND have been linked to chromosome 9p,
and both are types of FTLD-U. Thus, familial TDP-43 proteinopathy is associated with defects in multiple genes, and molecular
genetics is required in these cases to correctly identify the causative gene defect. In addition to genetic heterogeneity
amongst the TDP-43 proteinopathies, there is also neuropathologic heterogeneity and there is a close relationship between
genotype and FTLD-U subtype. In addition to these recent significant advances in the neuropathology of FTLD-U, novel FTLD
entities have been further characterized, including neuronal intermediate filament inclusion disease. The proposed criteria
incorporate up-to-date neuropathology of FTLD in the light of recent immunohistochemical, biochemical, and genetic advances.
These criteria will be of value to the practicing neuropathologist and provide a foundation for clinical, clinico-pathologic,
mechanistic studies and in vivo models of pathogenesis of FTLD. |
| |
Keywords: | Frontotemporal dementia Semantic dementia Progressive non-fluent aphasia Frontotemporal lobar degeneration Motor neuron disease Tauopathy Ubiquitin TDP-43 proteinopathy Progranulin Valosin-containing protein Charged multivesicular body protein 2B Neuronal intermediate filament inclusion disease Neuropathologic diagnosis |
本文献已被 PubMed SpringerLink 等数据库收录! |
|