Tau aggregation and its interplay with amyloid-β

Nisbet, Rebecca M., Polanco, Juan-Carlos, Ittner, Lars M. and Gotz, Jurgen (2014) Tau aggregation and its interplay with amyloid-β. Acta Neuropathologica, 129 2: 207-220. doi:10.1007/s00401-014-1371-2

Author Nisbet, Rebecca M.
Polanco, Juan-Carlos
Ittner, Lars M.
Gotz, Jurgen
Title Tau aggregation and its interplay with amyloid-β
Journal name Acta Neuropathologica   Check publisher's open access policy
ISSN 1432-0533
Publication date 2014-12-10
Year available 2014
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1007/s00401-014-1371-2
Open Access Status
Volume 129
Issue 2
Start page 207
End page 220
Total pages 14
Place of publication Heidelberg Germany
Publisher Springer
Collection year 2015
Language eng
Abstract Neurofibrillary tangles and amyloid plaques constitute the hallmark brain lesions of Alzheimer’s disease (AD) patients. Tangles are composed of fibrillar aggregates of the microtubule-associated protein tau, and plaques comprise fibrillar forms of a proteolytic cleavage product, amyloid-β (Aβ). Although plaques and tangles are the end-stage lesions in AD, small oligomers of Aβ and tau are now receiving increased attention as they are shown to correlate best with neurotoxicity. One key question of debate, however, is which of these pathologies appears first and hence is upstream in the pathocascade. Studies suggest that there is an intense crosstalk between the two molecules and, based on work in animal models, there is increasing evidence that Aβ, at least in part, exerts its toxicity via tau, with the Src kinase Fyn playing a crucial role in this process. In other experimental paradigms, Aβ and tau have been found to exert both separate and synergistic modes of toxicity. The challenge, however, is to integrate these different scenarios into a coherent picture. Furthermore, the ability of therapeutic interventions targeting just one of these molecules, to successfully neutralize the toxicity of the other, needs to be ascertained to improve current therapeutic strategies, such as immunotherapy, for the treatment of AD. Although this article is not intended to provide a comprehensive review of the currently pursued therapeutic strategies, we will discuss what has been achieved by immunotherapy and, in particular, how the inherent limitations of this approach can possibly be overcome by novel strategies that involve single-chain antibodies.
Keyword Alzheimer’s disease
Amyloid-β (Aβ)
Frontotemporal dementia
scFvs (single-chain variable antibody fragments)
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online ahead of print 10 Dec 2014

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Queensland Brain Institute Publications
Official 2015 Collection
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Citation counts: TR Web of Science Citation Count  Cited 21 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 20 times in Scopus Article | Citations
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