Atomic Resolution Structure of Monomorphic Aβ 42 Amyloid Fibrils

Amyloid-β (Aβ) is a 39-42 residue protein produced by the cleavage of the amyloid precursor protein (APP), which subsequently aggregates to form cross-β amyloid fibrils that are a hallmark of Alzheimer's disease (AD). The most prominent forms of Aβ are Aβ1-40 and Aβ1-42, which differ by two amino acids (I and A) at the C-terminus. However, Aβ42 is more neurotoxic and essential to the etiology of AD. Here, we present an atomic resolution structure of a monomorphic form of AβM01-42 amyloid fibrils derived from over 500 (13)C-(13)C, (13)C-(15)N distance and backbone angle structural constraints obtained from high field magic angle spinning NMR spectra. The structure (PDB ID: 5KK3 ) shows that the fibril core…

• DF
  Deutsche Forschungsgemeinschaft

  Award: SI2105/1-1
• V
  Vetenskapsrådet
• ER
  European Research Council
• NI
  National Institute of Biomedical Imaging and Bioengineering

  Awards: EB-002804, EB-003151, EB-002026