Neurodegenerative tauopathies

The defining neuropathological characteristics of Alzheimer's disease are abundant filamentous tau lesions and deposits of fibrillar amyloid beta peptides. Prominent filamentous tau inclusions and brain degeneration in the absence of beta-amyloid deposits are also hallmarks of neurodegenerative...

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Bibliographic Details
Published in:Annual review of neuroscience 2001-01, Vol.24 (1), p.1121-1159
Main Authors: LEE, Virginia M.-Y, GOEDERT, Michel, TROJANOWSKI, John Q
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Brain - pathology
Brain Diseases - genetics
Brain Diseases - pathology
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Dementia - genetics
Dementia - pathology
Humans
Medical sciences
Neurofibrillary Tangles - pathology
Neurology
tau Proteins - genetics
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Summary:The defining neuropathological characteristics of Alzheimer's disease are abundant filamentous tau lesions and deposits of fibrillar amyloid beta peptides. Prominent filamentous tau inclusions and brain degeneration in the absence of beta-amyloid deposits are also hallmarks of neurodegenerative tauopathies exemplified by sporadic corticobasal degeneration, progressive supranuclear palsy, and Pick's disease, as well as by hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Because multiple tau gene mutations are pathogenic for FTDP-17 and tau polymorphisms appear to be genetic risk factors for sporadic progressive supranuclear palsy and corticobasal degeneration, tau abnormalities are linked directly to the etiology and pathogenesis of neurodegenerative disease. Indeed, emerging data support the hypothesis that different tau gene mutations are pathogenic because they impair tau functions, promote tau fibrillization, or perturb tau gene splicing, thereby leading to formation of biochemically and structurally distinct aggregates of tau. Nonetheless, different members of the same kindred often exhibit diverse FTDP-17 syndromes, which suggests that additional genetic or epigenetic factors influence the phenotypic manifestations of neurodegenerative tauopathies. Although these and other hypothetical mechanisms of neurodegenerative tauopathies remain to be tested and validated, transgenic models are increasingly available for this purpose, and they will accelerate discovery of more effective therapies for neurodegenerative tauopathies and related disorders, including Alzheimer's disease.
ISSN:0147-006X
1545-4126
DOI:10.1146/annurev.neuro.24.1.1121