Pathogenic Aβ A2V versus protective Aβ A2T mutation: Early stage aggregation and membrane interaction

Laura Colombo, Alessio Gamba, Laura Cantù, Mario Salmona, Fabrizio Tagliavini, Valeria Rondelli, Elena Del Favero, Paola Brocca

Research output: Contribution to journalArticle

Abstract

We investigated the effects of punctual A-to-V and A-to-T mutations in the amyloid precursor protein APP, corresponding to position 2 of Aβ1-42. Those mutations had opposite effects on the onset and progression of Alzheimer disease, the former inducing early AD pathology and the latter protecting against the onset of the disease. We applied Static and Dynamic Light Scattering and Circular Dichroism, to study the different mutants in the early stages of the aggregation process, essential for the disease. Comparative results showed that the aggregation pathways differ in the kinetics and extent of the process, in the size of the aggregates and in the evolution of the secondary structure, resulting in fibrils of different morphology, as seen by AFM. Mutated peptides had comparable toxic effects on N2a cells. Moreover, as assessed by X-ray scattering, all of them displayed disordering effects on the internal structure of mixed phospholipids-gangliosides model membranes.

Original languageEnglish
Pages (from-to)11-18
Number of pages8
JournalBiophysical Chemistry
Volume229
DOIs
Publication statusPublished - Oct 2017

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Agglomeration
Membranes
Mutation
Amyloid beta-Protein Precursor
Gangliosides
Poisons
Circular Dichroism
Phospholipids
Alzheimer Disease
X-Rays
Pathology
Dynamic light scattering
X ray scattering
Peptides
Kinetics
Dynamic Light Scattering

Keywords

  • Alzheimer Disease
  • Amyloid beta-Peptides
  • Animals
  • Cell Line, Tumor
  • Cell Survival
  • Circular Dichroism
  • Dynamic Light Scattering
  • Humans
  • Kinetics
  • Lipid Bilayers
  • Mice
  • Microscopy, Atomic Force
  • Mutagenesis, Site-Directed
  • Peptide Fragments
  • Protein Aggregation, Pathological
  • Protein Binding
  • Protein Structure, Secondary
  • Recombinant Proteins
  • Scattering, Small Angle
  • X-Ray Diffraction
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Pathogenic Aβ A2V versus protective Aβ A2T mutation : Early stage aggregation and membrane interaction. / Colombo, Laura; Gamba, Alessio; Cantù, Laura; Salmona, Mario; Tagliavini, Fabrizio; Rondelli, Valeria; Del Favero, Elena; Brocca, Paola.

In: Biophysical Chemistry, Vol. 229, 10.2017, p. 11-18.

Research output: Contribution to journalArticle

Colombo, Laura ; Gamba, Alessio ; Cantù, Laura ; Salmona, Mario ; Tagliavini, Fabrizio ; Rondelli, Valeria ; Del Favero, Elena ; Brocca, Paola. / Pathogenic Aβ A2V versus protective Aβ A2T mutation : Early stage aggregation and membrane interaction. In: Biophysical Chemistry. 2017 ; Vol. 229. pp. 11-18.
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AU - Cantù, Laura

AU - Salmona, Mario

AU - Tagliavini, Fabrizio

AU - Rondelli, Valeria

AU - Del Favero, Elena

AU - Brocca, Paola

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