Targeting small Abeta oligomers: the solution to an Alzheimer's disease conundrum?
Amyloid beta (Abeta) is a small self-aggregating peptide produced at low levels by normal brain metabolism. In Alzheimer's disease (AD), self-aggregation of Abeta becomes rampant, manifested most strikingly as the amyloid fibrils of senile plaques. Because fibrils can kill neurons in culture, it has been argued that fibrils initiate the neurodegenerative cascades of AD. An emerging and different view, however, is that fibrils are not the only toxic form of Abeta, and perhaps not the neurotoxin that is most relevant to AD: small oligomers and protofibrils also have potent neurological activity. Immuno-neutralization of soluble Abeta-derived toxins might be the key to optimizing AD vaccines that are now on the horizon.
Klein
W L
WL
Northwestern University Institute for Neuroscience and Dept of Neurobiology and Physiology, Northwestern University, 2153 N Campus Drive, Evanston, IL 60208, USA. wklein@northwestern.edu
Krafft
G A
GA
Finch
C E
CE
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology; D016564:Amyloid beta-Protein Precursor / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000187:drug effects / Q000378:metabolism / Q000494:pharmacology; D058225:Plaque, Amyloid / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism*; D014612:Vaccines / Q000494:pharmacology / Q000627:therapeutic use
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000906:Antibodies; D010446:Peptide Fragments; D016708:Synaptophysin; D014612:Vaccines; C078592:amyloid beta-protein (1-40)