Accordingly, we report here that the alteration in APP binding to SorLA (and likely to other adaptors) leads to APP accumulation in LEs and lysosomes and to autophagic defects, which are considered a major risk factor for AD and dementia during aging (Cuervo, 2008; Salminen and Kaarniranta, 2009). The gene discussed is SORL1; the disease is dementia.