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. 2002 Nov;83(5):2610–2616. doi: 10.1016/S0006-3495(02)75271-5

Beta-amyloid 25 to 35 is intercalated in anionic and zwitterionic lipid membranes to different extents.

Silvia Dante 1, Thomas Hauss 1, Norbert A Dencher 1
PMCID: PMC1302346  PMID: 12414694

Abstract

Neuronal plasma membranes are thought to be the primary target of the neurotoxic beta-amyloid peptides (Abeta) in the pathogenesis of the Alzheimer's disease. Histologically, Abeta peptides are observed as extracellular macroscopic senile plaques, and most biophysical techniques have indicated the presence of Abeta close to the lipid headgroup region but not in the core of the membrane bilayers. The focus of this study is an investigation of the interaction between Abeta and lipid bilayers from a structural point of view. Neutron diffraction with the use of selectively deuterated amino acids has allowed us to determine unambiguously the position of the neurotoxic fragment Abeta (25-35) in the membrane. Two populations of the peptide are detected, one in the aqueous vicinity of the membrane surface and the second inside the hydrophobic core of the lipid membrane. The location of the C terminus was studied in two different lipid compositions and was found to be dependent on the surface charge of the membrane. The localization of beta-amyloid peptides in cell membranes will offer new insights on their mechanism in the neurodegenerative process associated with Alzheimer's disease and might provide clues for therapeutic developments.

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Selected References

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  1. Arispe N., Pollard H. B., Rojas E. Giant multilevel cation channels formed by Alzheimer disease amyloid beta-protein [A beta P-(1-40)] in bilayer membranes. Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10573–10577. doi: 10.1073/pnas.90.22.10573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beyreuther K., Masters C. L. Alzheimer's disease. The ins and outs of amyloid-beta. Nature. 1997 Oct 16;389(6652):677–678. doi: 10.1038/39479. [DOI] [PubMed] [Google Scholar]
  3. Bradshaw J. P., Davies S. M., Hauss T. Interaction of substance P with phospholipid bilayers: A neutron diffraction study. Biophys J. 1998 Aug;75(2):889–895. doi: 10.1016/S0006-3495(98)77577-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Busciglio J., Lorenzo A., Yeh J., Yankner B. A. beta-amyloid fibrils induce tau phosphorylation and loss of microtubule binding. Neuron. 1995 Apr;14(4):879–888. doi: 10.1016/0896-6273(95)90232-5. [DOI] [PubMed] [Google Scholar]
  5. Büldt G., Gally H. U., Seelig J., Zaccai G. Neutron diffraction studies on phosphatidylcholine model membranes. I. Head group conformation. J Mol Biol. 1979 Nov 15;134(4):673–691. doi: 10.1016/0022-2836(79)90479-0. [DOI] [PubMed] [Google Scholar]
  6. El-Agnaf O. M., Irvine G. B., Fitzpatrick G., Glass W. K., Guthrie D. J. Comparative studies on peptides representing the so-called tachykinin-like region of the Alzheimer Abeta peptide [Abeta(25-35)]. Biochem J. 1998 Dec 1;336(Pt 2):419–427. doi: 10.1042/bj3360419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Franks N. P., Lieb W. R. The structure of lipid bilayers and the effects of general anaesthetics. An x-ray and neutron diffraction study. J Mol Biol. 1979 Oct 9;133(4):469–500. doi: 10.1016/0022-2836(79)90403-0. [DOI] [PubMed] [Google Scholar]
  8. Haass C., De Strooper B. The presenilins in Alzheimer's disease--proteolysis holds the key. Science. 1999 Oct 29;286(5441):916–919. doi: 10.1126/science.286.5441.916. [DOI] [PubMed] [Google Scholar]
  9. Hauss T., Grzesiek S., Otto H., Westerhausen J., Heyn M. P. Transmembrane location of retinal in bacteriorhodopsin by neutron diffraction. Biochemistry. 1990 May 22;29(20):4904–4913. doi: 10.1021/bi00472a022. [DOI] [PubMed] [Google Scholar]
  10. Kohno T., Kobayashi K., Maeda T., Sato K., Takashima A. Three-dimensional structures of the amyloid beta peptide (25-35) in membrane-mimicking environment. Biochemistry. 1996 Dec 17;35(50):16094–16104. doi: 10.1021/bi961598j. [DOI] [PubMed] [Google Scholar]
  11. Mandelkow E. M., Mandelkow E. Tau in Alzheimer's disease. Trends Cell Biol. 1998 Nov;8(11):425–427. doi: 10.1016/s0962-8924(98)01368-3. [DOI] [PubMed] [Google Scholar]
  12. Mason R. P., Estermyer J. D., Kelly J. F., Mason P. E. Alzheimer's disease amyloid beta peptide 25-35 is localized in the membrane hydrocarbon core: x-ray diffraction analysis. Biochem Biophys Res Commun. 1996 May 6;222(1):78–82. doi: 10.1006/bbrc.1996.0699. [DOI] [PubMed] [Google Scholar]
  13. Mason R. P., Jacob R. F., Walter M. F., Mason P. E., Avdulov N. A., Chochina S. V., Igbavboa U., Wood W. G. Distribution and fluidizing action of soluble and aggregated amyloid beta-peptide in rat synaptic plasma membranes. J Biol Chem. 1999 Jun 25;274(26):18801–18807. doi: 10.1074/jbc.274.26.18801. [DOI] [PubMed] [Google Scholar]
  14. Mattson M. P., Cheng B., Davis D., Bryant K., Lieberburg I., Rydel R. E. beta-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity. J Neurosci. 1992 Feb;12(2):376–389. doi: 10.1523/JNEUROSCI.12-02-00376.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. McLaurin J., Chakrabartty A. Membrane disruption by Alzheimer beta-amyloid peptides mediated through specific binding to either phospholipids or gangliosides. Implications for neurotoxicity. J Biol Chem. 1996 Oct 25;271(43):26482–26489. doi: 10.1074/jbc.271.43.26482. [DOI] [PubMed] [Google Scholar]
  16. Mirzabekov T., Lin M. C., Yuan W. L., Marshall P. J., Carman M., Tomaselli K., Lieberburg I., Kagan B. L. Channel formation in planar lipid bilayers by a neurotoxic fragment of the beta-amyloid peptide. Biochem Biophys Res Commun. 1994 Jul 29;202(2):1142–1148. doi: 10.1006/bbrc.1994.2047. [DOI] [PubMed] [Google Scholar]
  17. Pike C. J., Burdick D., Walencewicz A. J., Glabe C. G., Cotman C. W. Neurodegeneration induced by beta-amyloid peptides in vitro: the role of peptide assembly state. J Neurosci. 1993 Apr;13(4):1676–1687. doi: 10.1523/JNEUROSCI.13-04-01676.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Selkoe D. J. Translating cell biology into therapeutic advances in Alzheimer's disease. Nature. 1999 Jun 24;399(6738 Suppl):A23–A31. doi: 10.1038/399a023. [DOI] [PubMed] [Google Scholar]
  19. Shao H., Jao S., Ma K., Zagorski M. G. Solution structures of micelle-bound amyloid beta-(1-40) and beta-(1-42) peptides of Alzheimer's disease. J Mol Biol. 1999 Jan 15;285(2):755–773. doi: 10.1006/jmbi.1998.2348. [DOI] [PubMed] [Google Scholar]
  20. Terzi E., Hölzemann G., Seelig J. Alzheimer beta-amyloid peptide 25-35: electrostatic interactions with phospholipid membranes. Biochemistry. 1994 Jun 14;33(23):7434–7441. doi: 10.1021/bi00189a051. [DOI] [PubMed] [Google Scholar]
  21. Terzi E., Hölzemann G., Seelig J. Interaction of Alzheimer beta-amyloid peptide(1-40) with lipid membranes. Biochemistry. 1997 Dec 2;36(48):14845–14852. doi: 10.1021/bi971843e. [DOI] [PubMed] [Google Scholar]
  22. Walter M. F., Mason P. E., Mason R. P. Alzheimer's disease amyloid beta peptide 25-35 inhibits lipid peroxidation as a result of its membrane interactions. Biochem Biophys Res Commun. 1997 Apr 28;233(3):760–764. doi: 10.1006/bbrc.1997.6547. [DOI] [PubMed] [Google Scholar]
  23. Wiener M. C., White S. H. Fluid bilayer structure determination by the combined use of x-ray and neutron diffraction. II. "Composition-space" refinement method. Biophys J. 1991 Jan;59(1):174–185. doi: 10.1016/S0006-3495(91)82209-3. [DOI] [PMC free article] [PubMed] [Google Scholar]

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