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Genetic dissection of Alzheimer's disease and related dementias: amyloid and its relationship to tau

Nature Neuroscience volume 1, pages 355–358 (1998)Cite this article

A Correction to this article was published on 01 December 1998

Abstract

Molecular genetic analysis is revealing the etiologies of Alzheimer's disease (AD) and related dementias. Here we review genetic and molecular biological evidence suggesting that the peptide Aβ42 is central to the etiology of AD. Recent data also suggests that dysfunction in the cytoskeletal protein tau is on the pathway that leads to neurodegeneration and dementia. Tau is produced either indirectly, by Aβ42, or directly, in some forms of frontotemporal dementia by mutations in tau itself. These data support and refine the amyloid cascade hypothesis for AD and suggest that understanding the causes and consquences of tau dysfunction is an important priority for dementia research.

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Figure 1: The amyloid cascade hypothesis, showing the proposed relationships between Aβ and tau and between Alzheimer's disease and FTDP-17.
Figure 2: The six major tau protein isoforms that are generated by alternative splicing of exons 2, 3 and 10.
Figure 3

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Acknowledgements

Supported by the Mayo Foundation and by an NIA Program Project Grant and an NINDS Project Grant (M.H.).

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Authors and Affiliations

  1. Neurogenetics and Transgenics Laboratories, Mayo Clinic Jacksonville, Jacksonville, 32224, Florida, USA

    John Hardy, Karen Duff, Katrina Gwinn Hardy, Jordi Perez-Tur & Mike Hutton

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Correspondence to John Hardy.

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Hardy, J., Duff, K., Hardy, K. et al. Genetic dissection of Alzheimer's disease and related dementias: amyloid and its relationship to tau. Nat Neurosci 1, 355–358 (1998). https://doi.org/10.1038/1565

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