Folia Neuropathologica
 
4/2005
 
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Tauopathies: recent insights into old diseases

Andre Delacourte

Folia Neuropathol 2005; 43 (4): 244-257
Neurofibrillary tangles are brain lesions that have been discovered at the beginning of the 20th century, using histological silver staining. Tangles are intra-neuronal hallmarks of a degenerating process: neurofibrillary degeneration (NFD). The basic component involved in tangle formation is tau protein. Tangles are found in more than 20 different neurodegenerative disorders, suggesting that NFD is a unique consequence to different types of etiological factors. However, tangles have a morphological and biochemical signature which is disease-specific. They are made up of different types of filaments such as paired helical filaments (PHFs) in Alzheimer’s disease or straight filaments in progressive supranuclear palsy. Tau aggregates have a disease-specific biochemical bar-code due to the aggregation of specific sets of tau isoforms. Tau lesions have also a disease-specific pattern of spatio-temporal progression in the human brain which is well correlated to cognitive impairment. At last, pathological tau mutations are at the origin of familial fronto-temporal diseases with parkinsonism (FTDP-17). Together, these observations have generated the concept of tauopathies. Indeed, each tauopathy is defined by a combination of clinical, neuropathological, biochemical and genetic features. Most of them have a specific defect on tau (mutation, aberrant splicing, abnormal phosphorylation, abnormal processing, neuronal or genotypic vulnerability), suggesting that, in fact, the etiology of most tauopathies is directly linked to tau dysfunction. In conclusion, we observe that most dementing disorders are tauopathies and that most demented patients have a tauopathy.
keywords:

Alzheimer’s diesease, tangles, tauopathy, amyloid, neurodegeneration

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