Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017;15(6):926-935.
doi: 10.2174/1570159X15666170116143743.

The Amyloid Cascade Hypothesis in Alzheimer's Disease: It's Time to Change Our Mind

Roberta Ricciarelli  1 , Ernesto Fedele  2
Affiliations
Review

The Amyloid Cascade Hypothesis in Alzheimer's Disease: It's Time to Change Our Mind

Roberta Ricciarelli et al. Curr Neuropharmacol. 2017.

Abstract

Since its discovery in 1984, the beta amyloid peptide has treaded the boards of neurosciences as the star molecule in Alzheimer's disease pathogenesis. In the last decade, however, this vision has been challenged by evidence-based medicine showing the almost complete failure of clinical trials that experimented anti-amyloid therapies with great hopes. Moreover, data have accumulated which clearly indicate that this small peptide plays a key role in the physiological processes of memory formation. In the present review, we will discuss the different aspects of the amyloid cascade hypothesis, highlighting its pros and cons, and we will analyse the results of the therapeutic approaches attempted to date that should change the direction of Alzheimer's disease research in the future.

Keywords: Alzheimer's disease; LTP; anti-amyloid therapy; beta amyloid; clinical trials; memory.

PubMed Disclaimer

Figures

Fig. (1)
Fig. (1)
The amyloidocentric theory of AD. The amyloid cascade hypothesis represented as the geocentric Ptolemy's theory of the solar system, which placed the Earth at the center and was accepted for many centuries.
See this image and copyright information in PMC

References

    1. Hardy J.A., Higgings G.A. Alzheimer’s disease: the amyloid cascade hypothesis. Science. 1992;256:184–185. [http://dx.doi.org/ 10.1126/science.1566067]. - PubMed
    1. Zhang X., Li Y., Xu H., Zhang Y. The γ-secreatse complex: from structure to function. Front. Cell. Neurosci. 2014;8:427. [http:// dx.doi.org/10.3389/fncel.2014.00427]. - PMC - PubMed
    1. Tiwari M.K., Kepp K.P. β-Amyloid pathogenesis: Chemical properties versus cellular levels. Alzheimers Dement. 2016;12:184–194. [http://dx.doi.org/10.1016/j.jalz.2015.06.1895]. - PubMed
    1. Mucke L., Selkoe D.J. Neurotoxicity of amylod β-protein: synaptic and network dysfunction. Cold Spring Harb. Perspect. Med. 2012;2:a006338. [http://dx.doi.org/10.1101/cshperspect. a006338]. - PMC - PubMed
    1. Ferreira S.T., Lourenco M.V., Oliveira M.M., De Felice F.G. Soluble amyloid-β oligomers as synaptotoxins leading to cognitive impairment in Alzheimer’s disease. Front. Cell. Neurosci. 2015;26:9–191. - PMC - PubMed

Substances