Clinic, neuropathology and molecular genetics of frontotemporal dementia: A mini-review

被引：35
作者：
Pan X.-D. [1 ,2 ,3 ]
Chen X.-C. [1 ,2 ,3 ]
机构：
[1] Department of Neurology, Union Hospital of Fujian Medical University, Fuzhou 350001
[2] Key Laboratory of Brain Aging and Neurodegenerative Disease, Fujian Institute of Geriatrics, Union Hospital of Fujian Medical University, Fuzhou 350001, 29 Xinquan, Road
[3] Centre of Neurobiology, Fujian Medical University, Fuzhou 350001
来源：
Translational Neurodegeneration | / 2卷 / 1期
基金：
中国国家自然科学基金;
关键词：
bvFTD; C9ORF72; GRN; Logopenic variant; MAPT; Molecular genetics; Nonfluent/agrammatic variant; Semantic variant;
D O I：
10.1186/2047-9158-2-8
中图分类号：
学科分类号：
摘要：
Frontotemporal lobar degeneration (FTLD) represents a group of clinically, neuropathologically and genetically heterogeneous disorders with plenty of overlaps between the neurodegenerative mechanism and the clinical phenotype. FTLD is pathologically characterized by the frontal and temporal lobar atrophy. Frontotemporal dementia (FTD) clinically presents with abnormalities of behavior and personality and language impairments variants. The clinical spectrum of FTD encompasses distinct canonical syndromes: behavioural variant of FTD (bvFTD) and primary progressive aphasia. The later includes nonfluent/agrammatic variant PPA (nfvPPA or PNFA), semantic variant PPA (svPPA or SD) and logopenic variant PPA (lvPPA). In addition, there is also overlap of FTD with motor neuron disease (FTD-MND or FTD-ALS), as well as the parkinsonian syndromes, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). The FTLD spectrum disorders are based upon the predominant neuropathological proteins (containing inclusions of hyperphosphorylated tau or ubiquitin protein, e.g transactive response (TAR) DNA-binding protein 43 kDa (TDP-43) and fusedin-sarcoma protein in neurons and glial cells) into three main categories: (1) microtubule-associated protein tau (FTLD-Tau); (2) TAR DNA-binding protein-43 (FTLD-TDP); and (3) fused in sarcoma protein (FTLD-FUS). There are five main genes mutations leading clinical and pathological variants in FTLD that identified by molecular genetic studies, which are chromosome 9 open reading frame 72 (C9ORF72) gene, granulin (GRN) gene, microtubule associated protein tau gene (MAPT), the gene encoding valosin-containing protein (VCP) and the charged multivesicular body protein 2B (CHMP2B). In this review, recent advances on the different clinic variants, neuroimaging, genetics, pathological subtypes and clinicopathological associations of FTD will be discussed. © 2013 Pan and Chen; licensee BioMed Central Ltd.
引用
收藏
相关论文
共 90 条
[11]  
Hou C.E., Yaffe K., Perez-Stable E.J., Miller B.L., Frequency of dementia etiologies in four ethnic groups, Dement Geriatr Cogn Disord, 22, pp. 42-47, (2006)
[12]  
Johnson J.K., Diehl J., Mendez M.F., Neuhaus J., Shapira J.S., Forman M., Chute D.J., Roberson E.D., Pace-Savitsky C., Neumann M., Frontotemporal lobar degeneration: demographic characteristics of 353 patients, Arch Neurol, 62, pp. 925-930, (2005)
[13]  
Piguet O., Hornberger M., Mioshi E., Hodges J.R., Behavioural-variant frontotemporal dementia: diagnosis, clinical staging, and management, Lancet Neurol, 10, pp. 162-172, (2011)
[14]  
Lillo P., Garcin B., Hornberger M., Bak T.H., Hodges J.R., Neurobehavioral features in frontotemporal dementia with amyotrophic lateral sclerosis, Arch Neurol, 67, pp. 826-830, (2010)
[15]  
Josephs K.A., Hodges J.R., Snowden J.S., Mackenzie I.R., Neumann M., Mann D.M., Dickson D.W., Neuropathological background of phenotypical variability in frontotemporal dementia, Acta Neuropathol, 122, pp. 137-153, (2011)
[16]  
Bathgate D., Snowden J.S., Varma A., Blackshaw A., Neary D., Behaviour in frontotemporal dementia, Alzheimer's disease and vascular dementia, Acta Neurol Scand, 103, pp. 367-378, (2001)
[17]  
Rascovsky K., Hodges J.R., Knopman D., Mendez M.F., Kramer J.H., Neuhaus J., van Swieten J.C., Seelaar H., Dopper E.G., Onyike C.U., Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia, Brain, 134, pp. 2456-2477, (2011)
[18]  
Rohrer J.D., Lashley T., Schott J.M., Warren J.E., Mead S., Isaacs A.M., Beck J., Hardy J., de Silva R., Warrington E., Clinical and neuroanatomical signatures of tissue pathology in frontotemporal lobar degeneration, Brain, 134, pp. 2565-2581, (2011)
[19]  
Grossman M., Primary progressive aphasia: clinicopathological correlations, Nat Rev Neurol, 6, pp. 88-97, (2010)
[20]  
Irwin D.J., McMillan C.T., Toledo J.B., Arnold S.E., Shaw L.M., Wang L.S., Van Deerlin V., Lee V.M., Trojanowski J.Q., Grossman M., Comparison of cerebrospinal fluid levels of tau and Abeta 1-42 in Alzheimer disease and frontotemporal degeneration using 2 analytical platforms, Arch Neurol, 69, pp. 1018-1025, (2012)
123456789