In the last two decades the amyloid cascade hypothesis of AD (Hardy and Higgins, 1992) has prevailed leading to accumulation of a significant amount of data on the molecular basis of the disease which have recently been reviewed by those who originally proposed the concept (Selkoe, 2001; Hardy, 2009) . From the clinical point of view, the disease is characterized by global cognitive decline, associated with brain pathology involving accumulation of extracellular amyloid aggregates (also known as senile plaques) of amyloid β peptide (Aβ) and intracellular neurofibrillary tangles of hyper-phosphorylated tau protein (Bothwell and Giniger, 2000) . According to the amyloid cascade hypothesis, it is the Aβ which is principally responsible for many of the pathological features of the disease (Hardy and Higgins, 1992; Sakono and Zako, 2010) with Aβ oligomers representing the most toxic species (Haass and Selkoe, 2007; Walsh and Selkoe, 2007; Sakono and Zako, 2010) . Accumulation of amyloid plaques is accompanied by astrogliosis and microgliosis (Grilli et al., 2003) and the most affected brain areas are the neocortex and hippocampus (Sisodia and Gallagher, 1998) . Although there are strong genetic links, including APP and presenilin mutations (Bothwell and Giniger, 2000) , as well as the apolipoprotein ε4 allele (Saunders et al., 1993; Deane et al., 2008; Huang, 2010) , sporadic AD is the dominant form. From this point of view predominance of AD research based on the mechanisms of early onset disease versus the broader spectrum of the factors leading to the sporadic form might be one of the reasons for the failure of the majority of therapeutic trials and lack of any preventive measures 20 years since the amyloid hypothesis has been proposed.