During amyloidogenesis, abeta peptides arise by successive cleavage of unprocessed APP by beta-and gamma-secretases [42], [43], [44], [45], [46], [47] and recently, it has come into question whether the large aggregated extracellular abeta plaques, a hallmark of AD pathology, directly cause the neurodegenerative effects in AD. This evidence concerns the gene APP and Alzheimer disease.