Accumulation of Alzheimer β-amyloid via Ganglioside Clusters

  • Katsumi Matsuzaki


Alzheimer’s disease (AD) is the most common form of dementia. The pathological hallmarks of AD brains are extracellular senile plaques and intracellular neurofibrillary tangles. It is widely accepted that the amyloid β-peptide (Aβ), which exists in fibrillar forms as a major component of senile plaques, is central to the development of AD. Aβ is a peptide composed of 40–42 amino acids (Fig. 1) and generated from proteolytic cleavage of amyloid precursor protein by β- and γ-secretases. Aβ is present at a very low concentration (<10 M) in biological fluids, and its physiological role is unknown. According to the so-called Aβ hypothesis, the conversion of soluble, nontoxic Aβ to aggregated toxic Aβ rich in β-sheet structures ignites the neurotoxic cascade(s) of Aβ. However, it is not clear how soluble Aβ forms aggregates.


Lipid Raft Small Unilamellar Vesicle Nordihydroguaiaretic Acid Alzheimer Amyloid Extracellular Senile Plaque 
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  1. Kakio A, Nishimoto S, Yanagisawa K, Kozutsumi Y, Matsuzaki K (2001) Cholesterol-dependent formation of GM1 ganglioside-bound amyloid β-protein, an endogenous seed for Alzheimer amyloid. J Biol Chem 276: 24985–24990PubMedCrossRefGoogle Scholar
  2. Kakio A, Nishimoto S, Yanagisawa K, Kozutsumi Y, Matsuzaki K (2002) Interactions of amyloid β-protein with various gangliosides in raft-like membranes: importance of GM1 ganglioside-bound form as an endogenous seed for Alzheimer amyloid. Biochemistry 41:7385–7390PubMedCrossRefGoogle Scholar
  3. Matsuzaki K (2007) Physicochemical interactions of amyloid β-peptide with lipid bilayers. Biochim Biophys Acta 1768:1935–1942PubMedCrossRefGoogle Scholar
  4. Matsuzaki K, Noguch T, Wakabayashi M, Ikeda K, Okada T, Ohashi Y, Hoshino M, Naiki H (2007) Inhibitors of amyloid β-protein aggregation mediated by GM1-containing raft-like membranes. Biochim Biophys Acta 1768:122–130PubMedCrossRefGoogle Scholar
  5. Wakabayashi M, Okada T, Kozutsumi Y, Matsuzaki K (2005) GM1 ganglioside-mediated accumulation of amyloid β-protein on cell membranes. Biochem Biophys Res Commun 328:1019–1023PubMedCrossRefGoogle Scholar
  6. Wakabayashi M, Matsuzaki K (2007) Formation of amyloids by Aβ-(1–42) on NGF-differentiated PC12 cells: roles of gangliosides and cholesterol. J Mol Biol 371:924–933PubMedCrossRefGoogle Scholar

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© Springer 2008

Authors and Affiliations

  • Katsumi Matsuzaki
    • 1
  1. 1.Graduate School of Pharmaceutical SciencesKyoto UniversityKyotoJapan

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