Distinct cerebrospinal fluid amyloid-beta peptide signatures in cognitive decline associated with Alzheimer's disease and schizophrenia

Abstract

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 (Aβ)1-42 in cerebrospinal fluid (CSF). To further clarify the role of Aβ in cognitive decline, we analyzed the whole panel of CSF Aβ 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 Aβ peptides. In CSF from SCZ, we detected an overall strong reduction of almost all Aβ species while in sporadic AD Aβ1-42 was the only peptide reduced. A significant independent association between Aβ1-40 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 Aβ and the most abundant Aβ1-40 isoform. These data suggests a dysmetabolism of amyloid precursor protein in older SCZ patients. Thus, the quite comparable reduction of CSF Aβ1-42 in AD and in elderly SCZ patients reflects different pathophysiological dynamics in ageing brain.