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Mechanisms of Neural and Behavioral Dysfunction in Alzheimer’s Disease

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Abstract

This review critically examines progress in understanding the link between Alzheimer’s disease (AD) molecular pathogenesis and behavior, with an emphasis on the impact of amyloid-β. We present the argument that the AD research field requires more multifaceted analyses into the impacts of Alzheimer’s pathogenesis which combine simultaneous molecular-, circuit-, and behavior-level approaches. Supporting this argument is a review of particular research utilizing similar, “systems-level” methods in mouse models of AD. Related to this, a critique of common physiological and behavioral models is made—highlighting the likely usefulness of more refined and specific tools in understanding the relationship between candidate molecular pathologies and behavioral dysfunction. Finally, we propose challenges for future research which, if met, may greatly extend our current understanding of how AD molecular pathology impacts neural network function and behavior and possibly may lead to refinements in disease therapeutics.

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Acknowledgments

We would like to thank two anonymous reviewers for kindly providing most thoughtful insights and critiques which improved this review.

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Authors and Affiliations

  1. Emotional Brain Institute, Nathan S. Kline Institute for Psychiatric Research, New York University School of Medicine, Orangeburg, NY, 10962, USA

    Daniel W. Wesson & Donald A. Wilson

  2. Center for Dementia Research, Nathan S. Kline Institute for Psychiatric Research, New York University School of Medicine, Orangeburg, NY, 10962, USA

    Ralph A. Nixon & Efrat Levy

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  1. Daniel W. Wesson
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  2. Ralph A. Nixon
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  4. Donald A. Wilson
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Correspondence to Daniel W. Wesson.

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Wesson, D.W., Nixon, R.A., Levy, E. et al. Mechanisms of Neural and Behavioral Dysfunction in Alzheimer’s Disease. Mol Neurobiol 43, 163–179 (2011). https://doi.org/10.1007/s12035-011-8177-1

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