Aberrant Co-localization of Synaptic Proteins Promoted by Alzheimer's Disease Amyloid-? Peptides: Protective Effect of Human Serum Albumin.

ABSTRACT: Amyloid-? (A?), A?40, A?42, and, recently, A?25-35 have been directly implicated in the pathogenesis of Alzheimer's disease. We have studied the effects of A? on neuronal death, reactive oxygen species (ROS) production, and synaptic assembling in neurons in primary culture. A?25-35, A?40, and A?42 significantly decreased neuronal viability, although A?25-35 showed a higher effect. A?25-35 showed a more penetrating ability to reach mitochondria while A?40 did not enter the neuronal cytosol and A?42 was scarcely internalized. We did not observe a direct correlation between ROS production and cell death because both A?40 and A?42 decreased neuronal viability but A?40 did not change ROS production. Rather, ROS production seems to correlate with the penetrating ability of each A?. No significant differences were found between A?40 and A?42 regarding the extent of the deleterious effects of both peptides on neuronal viability or synaptophysin expression. However, A?40 elicited a clear delocalization of PSD-95 and synaptotagmin from prospective synapsis to the neuronal soma, suggesting the occurrence of a crucial effect of A?40 on synaptic disassembling. The formation of A?40- or A?42-serum albumin complexes avoided the effects of these peptides on neuronal viability, synaptophysin expression, and PSD-95/synaptotagmin disarrangement suggesting that sequestration of A? by albumin prevents deleterious effects of these peptides. We can conclude that A? borne by albumin can be safely transported through body fluids, a fact that may be compulsory for A? disposal by peripheral tissues.

SUBMITTER: Dominguez-Prieto M 

PROVIDER: S-EPMC5115610 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature