Neurochemical Research

, Volume 31, Issue 9, pp 1153–1162

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

  • Pravat K. Mandal
  • Jay W. Pettegrew
  • Eliezer Masliah
  • Ronald L. Hamilton
  • Ratna Mandal
Original Paper

DOI: 10.1007/s11064-006-9140-9

Cite this article as:
Mandal, P.K., Pettegrew, J.W., Masliah, E. et al. Neurochem Res (2006) 31: 1153. doi:10.1007/s11064-006-9140-9

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.

Keywords

Parkinson’s diseaseAlzheimer’s diseaseDementia with Lewy bodiesAβ peptideα-SynNMR

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Pravat K. Mandal
    • 1
  • Jay W. Pettegrew
    • 1
  • Eliezer Masliah
    • 2
  • Ronald L. Hamilton
    • 3
  • Ratna Mandal
    • 1
  1. 1.Department of Psychiatry, Western Psychiatric Institute and ClinicUniversity of Pittsburgh Medical CenterPittsburghUSA
  2. 2.Department of NeuroscienceUniversity of CaliforniaSan DiegoUSA
  3. 3.Department of PathologyUniversity of Pittsburgh Medical CenterPittsburghUSA