1. Computational and Systems Biology
  2. Genetics and Genomics
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Alzheimer’s Disease: Exploring the origins of nucleation

  1. Katarzyna Marta Zoltowska
  2. Lucía Chávez-Gutiérrez  Is a corresponding author
  1. VIB-KU Leuven Center for Brain & Disease Research, Belgium
  2. Department of Neurosciences, Leuven Research Institute for Neuroscience and Disease (LIND), Belgium
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Cite this article as: eLife 2021;10:e67269 doi: 10.7554/eLife.67269
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Figures

Amyloid beta peptide and Alzheimer’s disease.

It is thought that Alzheimer’s disease is caused by amyloid beta (Aβ) (yellow circles; top) first forming dimers and then oligomers in a process called nucleation, with the oligomers then going on to build protofibrils and fibrils. Aggregated Aβ then deposits in amyloid plaques, which are a pathological hallmark of Alzheimer’s disease. Familial Alzheimer’s disease is hereditary and is marked by an unusually early onset of symptoms. Several genes have been linked to this form of the disease, including the gene for the amyloid precursor protein (APP). Certain amino acid residues in Aβ are called 'gatekeepers’ of nucleation (magenta stars; bottom) because they prevent nucleation. The mutations indicated (blue arrows), affecting amino acid residues highlighted in blue, cause familial Alzheimer’s disease or protect (A2T) against it. Pathogenic mutations in APP are shown in text (the numbering corresponds to the positions with Aβ). The sequence of amino acids shown here is from the N-terminal of Aβ42. Seuma et al. found that dominant pathogenic mutations within the Aβ42 peptide (indicated in bold text; bottom) all display increased rate of nucleation.

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