REVIEW: tau protein pathology in Alzheimer's disease and related disorders

Abundant neurofibrillary lesions made of hyperphosphorylated microtubule-associated protein tau constitute one of the defining neuropathological features of Alzheimer's disease. However, tau containing filamentous inclusions in neurones and/or glial cells also define a number of other neurodegenerative disorders clinically characterized by dementia and/or motor syndromes. All these disorders, therefore, are grouped under the generic term of tauopathies. In the first part of this review we outline the morphological and biochemical features of some major tauopathies, e. g. Alzheimer's disease, argyrophilic grain disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration. The impact of the recent finding of tau gene mutations in familial frontotemporal dementia and parkinsonism linked to chromosome 17 on other tauopathies is discussed in the second part. The review closes with a look towards a new understanding of neurodegenerative disorders characterized by filamentous nerve cell inclusions. The recent identification of the major protein component of their respective inclusions led to a surprising convergence of seemingly unrelated disorders. The new findings now allow us to classify neurodegenerative disorders with filamentous nerve cell inclusions into four main categories: (i) the tauopathies; (ii) the alpha-synucleinopathies; (iii) the polyglutamine disorders; and (iv) the iquitin disorders'. Within the proposed classification scheme, tauopathies constitute the most frequent type of disorder.