NFTs (neurofibrillary tangles) in Alzheimer's disease and in tauopathies are hallmark neuropathological lesions whose relationship with neuronal dysfunction, neuronal death and with other lesions [such as Aβ (amyloid β-peptide) pathology] are still imperfectly understood. Many transgenic mice overexpressing wild-type or mutant tau proteins have been generated to investigate the physiopathology of tauopathies. Most of the mice overexpressing wild-type tau do not develop NFTs, but can develop a severe axonopathy, whereas overexpression of mutant tau leads to NFT formation, synaptic loss and neuronal death in several models. The association between neuronal death and NFTs has, however, been challenged in some models showing a dissociation between tau aggregation and tau toxicity. Cross-breeding of mice developing NFTs with mice developing Aβ deposits increases NFT pathology, highlighting the relationship between tau and amyloid pathology. On the other hand, tau expression seems to be necessary for expression of a pathological phenotype associated with amyloid pathology. These findings suggest that there is a bilateral cross-talk between Aβ and tau pathology. These observations are discussed by the presentation of some relevant models developed recently.
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Conference Article| July 26 2010
Modulation of tau pathology in tau transgenic models
Jean-Pierre Brion 1
1Laboratory of Histology, Neuroanatomy and Neuropathology, Université Libre de Bruxelles, 808 route de Lennik, B-1070 Brussels, Belgium
1To whom correspondence should be addressed (email email@example.com).
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Jean-Pierre Brion, Kunie Ando, Céline Heraud, Karelle Leroy; Modulation of tau pathology in tau transgenic models. Biochem Soc Trans 1 August 2010; 38 (4): 996–1000. doi: https://doi.org/10.1042/BST0380996
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