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Interaction between Aβ Peptide and α Synuclein: Molecular Mechanisms in Overlapping Pathology of Alzheimer’s and Parkinson’s in Dementia with Lewy Body Disease

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An Erratum to this article was published on 12 June 2007

Abstract

Amyloidogenic proteins (Aβ peptide) in Alzheimer’s disease (AD) and alpha-synuclein (α-Syn) in Parkinson’s disease (PD) are typically soluble monomeric precursors, which undergo remarkable conformational changes and culminate in the form of aggregates in diseased condition. Overlap of clinical and neuropathological features of both AD and PD are observed in dementia with Lewy body (DLB) disease, the second most common form of dementia after AD. The identification of a 35-amino acid fragment of α-Syn in the amyloid plaques in DLB brain have raised the possibility that Aβ and α-Syn interact with each other. In this report, the molecular interaction of α-Syn with Aβ40 and/or Aβ42 are investigated using multidimensional NMR spectroscopy. NMR data in the membrane mimic environment indicate specific sites of interaction between membrane-bound α-Syn with Aβ peptide and vice versa. These Aβ–α-Syn interactions are demonstrated by reduced amide peak intensity or change in chemical shift of amide proton of the interacting proteins. Based on NMR results, the plausible molecular mechanism of overlapping pathocascade of AD and PD in DLB due to interactions between α-Syn and Aβ is described. To the best of our knowledge, it is the first report using multidimensional NMR spectroscopy that elucidates molecular interactions between Aβ and α-Syn which may lead to onset of DLB.

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Acknowledgments

Pravat K Mandal thanks to Dr David J. Kupfer, MD (Chairman, Psychiatry) for encouragement and support. Financial support in the form of research grants from American Parkinson Disease Association and Alzheimer Disease Research Center, University of Pittsburgh and American Health Assistance Foundation are appreciated.

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Authors and Affiliations

  1. Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, 3811 O’Hara Street, Pittsburgh, PA, 15213, USA

    Pravat K. Mandal, Jay W. Pettegrew & Ratna Mandal

  2. Department of Neuroscience, University of California, San Diego, CA, USA

    Eliezer Masliah

  3. Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA , 15213, USA

    Ronald L. Hamilton

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  1. Pravat K. Mandal
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Correspondence to Pravat K. Mandal.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s11064-007-9391-0

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Mandal, P.K., Pettegrew, J.W., Masliah, E. et al. Interaction between Aβ Peptide and α Synuclein: Molecular Mechanisms in Overlapping Pathology of Alzheimer’s and Parkinson’s in Dementia with Lewy Body Disease. Neurochem Res 31, 1153–1162 (2006). https://doi.org/10.1007/s11064-006-9140-9

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