Consistent with the idea that SIRT2 can protect against neurodegenerative pathology in mouse models of Alzheimer's disease, overactivation of SIRT2 has been shown to protect against axonopathy and neurodegeneration in a mouse model of Wallerian degeneration (Arraki et al., 2004; Tang and Chua, 2008). Here, SIRT2 is linked to early-onset autosomal dominant Alzheimer disease.