Amyotrophic lateral sclerosis, frontotemporal dementia and beyond: the TDP-43 diseases

作者：Geser Felix^*; Martinez Lage Maria; Kwong Linda K; Lee Virginia M Y; Trojanowski John Q

来源：Journal of Neurology, 2009, 256(8): 1205-1214.

DOI：10.1007/s00415-009-5069-7

• Amyotrophic lateral sclerosis (ALS)
• Frontotemporal dementia
• TDP-43 proteinopathy

Ever since the significance of pathological 43-kDa transactivating responsive sequence DNA-binding protein (TDP-43) for human disease has been recognized in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin positive inclusions (FTLD-U), a number of publications have emerged reporting on this pathology in a variety of neurodegenerative diseases. Given the heterogeneous and, in part, conflicting nature of the recent findings, we here review pathological TDP-43 and its relationship to human disease with a special focus on ALS and FTLD-U. To this end, we propose a classification scheme in which pathological TDP-43 is the major disease defining pathology in one group, or is present in addition to other neurodegenerative hallmark pathologies in a second category. We conclude that the TDP-43 proteinopathies represent a novel class of neurodegenerative disorders akin to alpha-synucleinopathies and tauopathies, with the concept of ALS and FTLD-U to be widened to a broad clinico-pathological multisystem disease, i.e., TDP-43 proteinopathy.

• 出版日期2009-8