Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Alzheimer Disease / drug therapy
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Alzheimer Disease / metabolism*
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Amyloid beta-Peptides / drug effects
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Amyloid beta-Peptides / metabolism*
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Amyloid beta-Peptides / pharmacology
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Amyloid beta-Protein Precursor / drug effects
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Amyloid beta-Protein Precursor / metabolism*
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Animals
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Antibodies / pharmacology
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Antibodies / therapeutic use
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Hippocampus / drug effects
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Hippocampus / metabolism
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Long-Term Potentiation / drug effects
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Long-Term Potentiation / physiology
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Mice
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Mice, Transgenic
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Peptide Fragments / drug effects
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Peptide Fragments / metabolism
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Peptide Fragments / pharmacology
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Plaque, Amyloid / drug effects
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Plaque, Amyloid / metabolism
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Synaptophysin / metabolism*
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Vaccines / pharmacology
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Vaccines / therapeutic use
Substances
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Amyloid beta-Peptides
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Amyloid beta-Protein Precursor
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Antibodies
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Peptide Fragments
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Synaptophysin
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Vaccines
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amyloid beta-protein (1-40)