Mild alterations in cognitive function are present in normal aging and severe cognitive alterations are a hallmark of Alzheimer's disease (AD). Cognitive deficits are prevalent in patients with schizophrenia (SCZ) and worsen with old age. We recently reported that elderly SCZ patients show reduced levels of amyloid-beta (A beta)142 in cerebrospinal fluid (CSF). To further clarify the role of A beta in cognitive decline, we analyzed the whole panel of CSF A beta isoforms in elderly SCZ patients as well as in sporadic AD using SELDI TOF MS. The immunoproteomic study revealed, in all analyzed CSF samples, the presence of 15 different A beta peptides. In CSF from SCZ, we detected an overall strong reduction of almost all A beta species while in sporadic AD A beta 142 was the only peptide reduced. A significant independent association between A beta 140 levels and global cognition was found in SCZ. In addition, in SCZ patients, duration of therapy was positively associated with soluble amyloid precursor protein alpha levels, the total amount of CSF A beta and the most abundant A beta 140 isoform. These data suggests a dysmetabolism of amyloid precursor protein in older SCZ patients. Thus, the quite comparable reduction of CSF A beta 142 in AD and in elderly SCZ patients reflects different pathophysiological dynamics in ageing brain.