Reversible in vitro growth of Alzheimer disease β-amyloid plaques by deposition of labeled amyloid peptide

J. E. Maggio, E. R. Stimson, J. R. Ghilardi, C. J. Allen, C. E. Dahl, D. C. Whitcomb, S. R. Vigna, H. V. Vinters, M. E. Labenski, P. W. Mantyh

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Abstract

The salient pathological feature of Alzheimer disease (AD) is the presence of a high density of amyloid plaques in the brain tissue of victims. The plaques are predominantly composed of human β-amyloid peptide (βA4), a 40- mer whose neurotoxicity is related to its aggregation. Radioiodinated human βA4 is rapidly deposited in vitro from a dilute (<10 pM) solution onto neuritic and diffuse plaques and cerebrovascular amyloid in AD brain tissue, whereas no deposition is detectable in tissue without preformed plaques. This growth of plaques by deposition of radiolabeled βA4 to plaques is reversible, with a dissociation half-time of ≃1 h. The fraction of grey matter occupied by plaques that bind radiolabeled βA4 in vitro is dramatically larger in AD cortex (23 ± 11%) than in age-matched normal controls (<2%). In contrast to the human peptide, rat/mouse βA4 (differing at three positions from human βA4) does not affect the deposition of radiolabeled human βA4. βA4 has no detectable interaction with tachykinin receptors in rat or human brain. The use of radioiodinated βA4 provides an in vitro system for the quantitative evaluation of agents or conditions that may inhibit or enhance the growth or dissolution of AD plaques. This reagent also provides an extremely sensitive method for visualizing various types of amyloid deposits and a means for characterizing and locating sites of amyloid peptide binding to cells and tissues.

Original languageEnglish (US)
Pages (from-to)5462-5466
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number12
DOIs
StatePublished - 1992

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    Maggio, J. E., Stimson, E. R., Ghilardi, J. R., Allen, C. J., Dahl, C. E., Whitcomb, D. C., Vigna, S. R., Vinters, H. V., Labenski, M. E., & Mantyh, P. W. (1992). Reversible in vitro growth of Alzheimer disease β-amyloid plaques by deposition of labeled amyloid peptide. Proceedings of the National Academy of Sciences of the United States of America, 89(12), 5462-5466. https://doi.org/10.1073/pnas.89.12.5462