Although previous work has shown that reducing both WT and mutant ATXN1 protein levels can rescue disease phenotypes in an SCA1 mouse model (13–15), it is critical to reduce mutant ATXN1 specifically for the following reasons: (1) loss of WT ATXN1 can potentiate AD by increasing Aβ deposition (16); (2) WT ATXN1 is protective for SCA1 (17); (3) selective reduction of mutant ATXN1 is more effective in rescuing disease phenotype than targeting both mutant and WT protein (18). This evidence concerns the gene ATXN1 and Alzheimer disease.