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John Hardy on With PLD3, Forget APP...Think Lysosome Instead

COMMENT This paper from the De Strooper lab convincingly shows that there is not a clear effect of PLD3 on APP biology and reignites the debate on whether PLD3 is an AD gene (Cruchaga et al., 2013). Genetic analysis looking for rare variants is subject to ...

John Hardy on γ-Secretase Revealed in Atomic Glory

COMMENT I agree with Sam Sisodia that assessing the structure of other mutations would be useful. An obvious one is the D9 mutation which has a clear effect on function (Perez-Tur et al., 1995; Thinakaran et al., 1996). J.Hardy 0 A mutation in Alzheimer's ...

Rita Guerreiro, John Hardy on γ-Secretase Revealed in Atomic Glory

COMMENT This study by Bai and colleagues resolves the γ-secretase structure to an atomic level (resolution of 3.4Ǻ). This type of detail allows the authors to map and analyze some of the reported PSEN1 disease-associated mutations and to start to develop clearer ...

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