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. A recessive mutation in the APP gene with dominant-negative effect on amyloidogenesis. Science. 2009 Mar 13;323(5920):1473-7. PubMed.

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  1. There may be a reversible formation of dimers in the APP molecule, before being cleaved by γ-secretase and the subsequent formation of Aβ dimers, thus preserving the molecule for cleavage by α-secretase.

    Data provided by this extraordinary article based on a mutation of the amino-terminal region of Aβ in its precursor molecule APP (changes in its primary sequence trigger peptide assembly and fibril formation) point to this possibility, since the relationship between the carboxy-terminal fragments generated by β- and α-secretase (1.9 ± 0.2 increase in C99: C83 ratio in patient's fibroblasts) implies double the rate of β product versus α in the mutant APP.

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