spectrum disease; the former labeled type 1 and the latter type 2 small vessel disease (Pantoni, 2010). Both types of arteriopathies make dementia patients vulnerable to hemodynamic fluctuation through impairments in cerebral autoregulation and vascular reactivity (Tanoi et al., 2000; Pimentel-Coelho and Rivest, 2012). Consequently, hypoperfusion induces Aβ overproduction and elimination failure (Zlokovic, 2011; Carare et al., 2013; Elali et al., 2013). Brain ischemia and hypoxia modulates amyloid precursor protein (APP) cleavage enzymes such as β-secretase and γ-secretase, thereby resulting in increased Aβ production (Sun et al., 2006; Guglielmotto et al., 2009; Kitaguchi et al., 2009; Li et al., 2009). Excess Aβ contributes to the impairment of Aβ clearance and CAA (Joachim et al., 1989; Rovelet-Lecrux et al., 2006; Han et al., 2008). Aβ elimination failure could also result from arteriolosclerosis (Weller et al., 2009). Thus, dementia patients with a single simple etiology are scarcely seen, except for juvenile familial AD cases caused by mutations in the APP or presenilin genes, comprising <1% of AD cases (Campion et al., 1999).
