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Is Alzheimer’s a Disorder of Ageing and Why Don’t Mice get it? The Centrality of Insulin Signalling to Alzheimer’s Disease Pathology

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Diabetes, Insulin and Alzheimer's Disease

Part of the book series: Research and Perspectives in Alzheimer's Disease ((ALZHEIMER))

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Abstract

The amyloid cascade hypothesis has had considerable importance in driving forward the molecular understanding of Alzheimer’s disease (AD) pathology. One component of that cascade might be glycogen synthase kinase-3 (GSK3), a kinase that appears to be activated by Aβ and in turn phosphorylates tau. GSK3 is also inhibited by insulin signalling and insulin resistance, and diabetes is a major risk factor for AD. We hypothesise, as others have done, that insulin signalling is central to the pathological process, with evidence that both genetic and environmental risk factors for AD involve the insulin pathway. We also postulate that transgenic mice provide only a partial model for AD, as insulin signalling acts as a protective factor against Aβ toxicity; also, the well-established relationship between insulin signalling and longevity might explain why the single most important risk factor for AD is age.

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  1. Institute of Psychiatry, King’s College London, De Crespigny Park, London, SE5 8AF, UK

    Simon Lovestone & Richard Killick

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  1. Simon Lovestone
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  1. School of Medicine, University of Washington, S. Columbian Way 1660, Seattle, 98108, USA

    Suzanne Craft

  2. Recherche Therapeutique, Fondation IPSEN pour la, quai George Gorse 65, Boulogne Billancourt Cedex, 92650, France

    Yves Christen

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Lovestone, S., Killick, R. (2010). Is Alzheimer’s a Disorder of Ageing and Why Don’t Mice get it? The Centrality of Insulin Signalling to Alzheimer’s Disease Pathology. In: Craft, S., Christen, Y. (eds) Diabetes, Insulin and Alzheimer's Disease. Research and Perspectives in Alzheimer's Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-04300-0_9

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