APP and Cognitive impairment: There is a plethora of evidence that support the Aβ hypothesis: patients with an extra copy of chromosome 21, where the APP gene locates, develop dementia at an early age; APP transgenic mice exhibit significant cognitive impairment; the toxicity of Aβ has been documented extensively in in vitro studies (Del Bo et al., 1995; Combs et al., 2001; Wicklund et al., 2010).