SPAST and Alzheimer disease: Thus, in a formal sense, the view that microtubule severing by spastin might be impaired in HSP (i.e. under-activity of spastin) is the opposite to our proposed pathological cascade of AD, which involves aberrant microtubule breakdown by spastin (i.e. over-activity of spastin; Fig. 2b, c, Fig. 3c).