Familial Alzheimer's mutations within APPTM increase Aβ42 production by enhancing accessibility of ε-cleavage site.

@article{Chen2014FamilialAM,
  title={Familial Alzheimer's mutations within APPTM increase Aβ42 production by enhancing accessibility of ε-cleavage site.},
  author={Wen Chen and Eric Gamache and David J Rosenman and Jian Xie and Maria Marta L{\'o}pez and Yue-Ming Li and Chunyu Wang},
  journal={Nature communications},
  year={2014},
  volume={5},
  pages={3037}
}
The high Aβ42/Aβ40 production ratio is a hallmark of familial Alzheimer's disease, which can be caused by mutations in the amyloid precursor protein (APP). The C-terminus of Aβ is generated by γ-secretase cleavage within the transmembrane domain of APP (APPTM), a process that is primed by an initial ε-cleavage at either T48 or L49, resulting in subsequent production of Aβ42 or Aβ40, respectively. Here we solve the dimer structures of wild-type APPTM (AAPTM WT) and mutant APPTM (FAD mutants V44M… CONTINUE READING
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The NMR structural coordinates and constraints of the wild-type and V44M APP-TM proteins have been deposited in the protein databank under accession codes 2LZ3 (WT) and 2LZ4 (V44M)

  • A. Bhattacharya, R. Tejero, +6 authors W. C. wrote the paper. Additional information Accessi codes
  • Competing financial interests: The authors…
  • 2014

Alzheimer’s disease mutations in APP but not gammasecretase modulators affect epsilon-cleavage-dependent AICD production

  • M Dimitrov
  • Nat. Commun
  • 2013

The mechanism of gamma-Secretase dysfunction in familial Alzheimer disease

  • L Chavez-Gutierrez
  • EMBO J. 31,
  • 2012

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