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 ...

John Hardy on Good Gene, Bad Gene?—New APP Variant May Be Both

COMMENT The identification of two families with homozygous APP variants (Tomiyama et al., 2008 and now Di Fede et al., 2009) is interesting, but the linkage analysis in neither pedigree is sufficient for us to be sure that the mutations are pathogenic, let alone ...

John Hardy on SORLA Soars—Large Study Links Gene to Late-onset AD

COMMENT This work is welcome news from an excellent group of investigators. They will surely allow me to play devil’s advocate and caution two things. First, however enticing the cell biology might be, at this point it is a distraction. The question at hand is a ...

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