Brain amyloid beta protein and memory disruption in Alzheimer's disease

The development of amyloid-containing neuritic plaques is an invariable characteristic of Alzheimer's diseases (AD). The conversion from monomeric amyloid beta protein (A beta) to oligomeric A beta and finally neuritic plaques is highly dynamic. The specific A beta species that is correlated with disease severity remains to be discovered. Oligomeric A beta has been detected in cultured cells, rodent and human brains, as well as human cerebrospinal fluid. Synthetic, cell, and brain derived A beta oligomers have been found to inhibit hippocampal long-term potentiation (LTP) and this effect can be suppressed by the blockage of A beta oligomer formation. A large body of evidence suggests that A beta oligomers inhibit N-methyl-D-aspartate receptor dependent LTP; additional receptors have also been found to elicit downstream pathways upon binding to A beta oligomers. Amyloid antibodies and small molecular compounds that reduce brain A beta levels and block A beta oligomer formation are capable of reversing synaptic dysfunction and these approaches hold a promising therapeutic potential to rescue memory disruption.