Intracellular biology of Alzheimer's disease amyloid beta peptide

Strong evidence links excess production of a small peptide and the pathogenesis of Alzheimer's disease (AD). Originally this peptide, beta-amyloid 42 (A beta 42), was assumed to be released by a pathogenic event; it is now well established that A beta 42 is released from cells during normal cellular metabolism of the Alzheimer amyloid precursor protein. Recently, in a series of surprising reports it was discovered that A beta 42 is produced intracellularly, and what might have been regarded first as a strange abnormality of a few selected cell lines has now been recognized as an important cellular pathway for A beta production. Moreover, the differences between secretory and intracellular A beta production might hold the clues for brain specificity and cellular mechanisms of AD pathogenesis.