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Neuroimaging Results Impose New Views on Alzheimer’s Disease—the Role of Amyloid Revised

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Abstract

Huge progress has been made in unraveling the mysteries of Alzheimer’s disease (AD), but we still do not understand the basic mechanisms that set off the cascade of pathological events. In May 2011, the National Institute on Aging–Alzheimer’s Association published new diagnostic guidelines, expected to have huge impact on AD research and clinical practice. However, the new guidelines are already criticized for being biased in favor of a specific theory of the pathophysiological origins of AD—the amyloid cascade hypothesis. Shortly before publication of the guidelines, a hypothetical model of the dynamic biomarkers of the Alzheimer’s pathological cascade was published, taking as starting point that biomarkers reflecting brain levels of amyloid become deviant long before brain atrophy, cognitive dysfunction, or clinical symptoms are manifest. This model has already attracted substantial interest and arguably represents a dominating view within human research on AD. Here we critically review the evidence for the view of amyloid as an initiating event in the pathological cascade and discuss how central assumptions of this hypothesis affect how results from contemporary human AD research are understood. Interpretations of new results are greatly impacted by researchers’ view on the role of amyloid, and identical observations are sometimes taken to support radically opposing views on the amyloid hypothesis. We argue that the canonical view of the role of amyloid as the main causal factor in AD may not be correct and that evidence from recent neuroimaging studies indicates that amyloid is neither necessary nor sufficient, for the manifestation of AD-like brain atrophy.

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Acknowledgments

This work was supported by grants from the Norwegian Research Council to Kristine B Walhovd (grant nos. 177404, 186092, and 192663) and Anders M Fjell (nos. 175066 and 189507).

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  1. Center for the Study of Human Cognition, Department of Psychology, University of Oslo, Pb. 1094 Blindern, 0317, Oslo, Norway

    Anders M. Fjell & Kristine B. Walhovd

  2. Unit of Neuropsychology, Department of Physical Medicine and Rehabilitation, Oslo University Hospital, Oslo, Norway

    Anders M. Fjell & Kristine B. Walhovd

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  1. Anders M. Fjell
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Correspondence to Anders M. Fjell.

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Fjell, A.M., Walhovd, K.B. Neuroimaging Results Impose New Views on Alzheimer’s Disease—the Role of Amyloid Revised. Mol Neurobiol 45, 153–172 (2012). https://doi.org/10.1007/s12035-011-8228-7

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