Prion-Like Properties of Assembled Tau Protein
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The soluble microtubule-associated protein tau becomes hyperphosphorylated, insoluble and filamentous in a number of neurodegenerative diseases collectively referred to as tauopathies. In Alzheimer’s disease (AD), tau pathology develops in a stereotypical manner, with the first lesions appearing in the locus coeruleus and the transentorhinal cortex, from where they appear to spread to the entorhinal cortex, the hippocampus and the neocortex. The staging of tau pathology has also been described in argyrophilic grain disease (AGD), where tau lesions spread stereotypically throughout the limbic system. The isoform composition and morphology of tau filaments differ between diseases, suggesting the possible existence of different tau strains, reminiscent of prion strains. Prion diseases result from the misfolding of the cellular prion protein that can occur sporadically, as the result of dominantly inherited mutations or following infection. Recent experimental work has shown that prion-like mechanisms are also at work in the tauopathies.
KeywordsEntorhinal Cortex Braak Stage Argyrophilic Grain Disease Transentorhinal Cortex Posterior Medial Temporal Lobe
- Allen B, Ingram E, Takao M, Smith MJ, Jakes R, Virdee K, Yoshida H, Holzer M, Craxton M, Emson PC, Atzori C, Migheli A, Crowther RA, Ghetti B, Spillantini MG, Goedert M (2002) Abundant tau filaments and nonapoptotic neurodegeneration in transgenic mice expressing human P301S tau protein. J Neurosci 22:9340–9351PubMedGoogle Scholar
- Bugiani O, Murrell JR, Giaccone G, Hasegawa M, Ghigo G, Tabaton M, Morbin M, Primavera A, Carella F, Solaro C, Grisoli M, Savoiardo M, Spillantini MG, Tagliavini F, Goedert M, Ghetti B (1999) Frontotemporal dementia and corticobasal degeneration in a family with a P301S mutation in tau. J Neuropathol Exp Neurol 58:667–677PubMedCrossRefGoogle Scholar
- Hutton M, Lendon CL, Rizzu P, Baker M, Froelich S, Houlden H, Pickering-Brown S, Chakraverty S, Isaacs A, Grover A, Hackett J, Adamson J, Lincoln S, Dickson D, Davies P, Petersen RC, Stevens M, de Graaff E, Wauters E, van Baren J, Hillebrand M, Joosse M, Kwon JM, Nowotny P, Che LK, Norton J, Morris JC, Reed LA, Trojanowski J, Basun H, Lannfelt L, Neystat M, Fahn S, Dark F, Tannenberg T, Dodd PR, Hayward N, Kwok JB, Schofield PR, Andreadis A, Snowden J, Craufurd D, Neary D, Owen F, Oostra BA, Hardy J, Goate A, van Swieten J, Mann D, Lynch T, Heutink P (1998) Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393:702–705PubMedCrossRefGoogle Scholar
- Probst A, Götz J, Wiederhold KH, Tolnay M, Mistl C, Jaton AL, Hong M, Ishihara T, Lee VM, Trojanowski JQ, Jakes R, Crowther RA, Spillantini MG, Bürki K, Goedert M (2000) Axonopathy and amyotrophy in mice transgenic for human four-repeat tau protein. Acta Neuropathol 99:469–481PubMedCrossRefGoogle Scholar