Targeting small A beta oligomers: the solution to an Alzheimer's disease conundrum?

Amyloid beta (A beta) is a small self-aggregating peptide produced at low l evels by normal brain metabolism. In Alzheimer's disease (AD), self-aggrega tion of A beta becomes rampant, manifested most strikingly as the amyloid f ibrils of senile plaques. Because fibrils can kill neurons in culture, it h as been argued that fibrils initiate the neurodegenerative cascades of AD. An emerging and different view, however, is that fibrils are not the only t oxic form of A beta, and perhaps not the neurotoxin that is most relevant t o AD: small oligomers and protofibrils also have potent neurological activi ty. Immuno-neutralization of soluble A beta -derived toxins might be the ke y to optimizing AD vaccines that are now on the horizon.