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Targeting Alzheimer amyloid plaques in vivo

Nature Biotechnology volume 18, pages 868–872 (2000)Cite this article

Abstract

The only definitive diagnosis for Alzheimer disease (AD) at present is postmortem observation of neuritic plaques and neurofibrillary tangles in brain sections. Radiolabeled amyloid-β peptide (Aβ), which has been shown to label neuritic plaques in vitro, therefore could provide a diagnostic tool if it also labels neuritic plaques in vivo following intravenous injection. In this study, we show that the permeability of Aβ at the blood–brain barrier can be increased by at least twofold through covalent modification with the naturally occurring polyamine, putrescine. We also show that, following intravenous injection, radiolabeled, putrescine-modified Aβ labels amyloid deposits in vivo in a transgenic mouse model of AD, as well as in vitro in human AD brain sections. This technology, when applied to humans, may be used to detect plaques in vivo, allowing early diagnosis of the disease and therapeutic intervention before cognitive decline occurs.

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Figure 1: RP-HPLC chromatograms of unlabeled Aβ 1-40 (A) and PUT-Aβ 1-40 (B).
Figure 2: 125I-Aβ 1-40 and 125I-PUT-Aβ 1-40 labeling of amyloid deposits in vitro: Film autoradiography.
Figure 3: 125I-Aβ 1-40 and 125I-PUT-Aβ 1-40 labeling of amyloid deposits in vitro with equivalent radioactivity.
Figure 4: 125I-Aβ 1-40 and 125I-PUT-Aβ 1-40 labeling of amyloid deposits in vitro in the absence or presence of a 10-fold excess of unbound putrescine.
Figure 5: 125I-PUT-Aβ 1-40 labeling of amyloid deposits in vivo in APP, PS1 transgenic mouse brain.

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Acknowledgements

The authors wish to thank Dr. Shirley Poduslo for her generous gift of human AD brain tissue, Dr. Karen Duff for her generous gift of PS1 transgenic mice, and Dr. John Maggio for his valuable technical advice. The authors also wish to thank Shelly Whelan for her expert technical assistance and Jennifer Scott for her expert secretarial assistance.

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  1. Departments of Neurology Biochemistry/Molecular Biology, Molecular Neurobiology Laboratory, Mayo Clinic and Foundation, Rochester, 55905, MN

    Thomas M. Wengenack, Geoffry L. Curran & Joseph F. Poduslo

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  1. Thomas M. Wengenack
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  2. Geoffry L. Curran
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  3. Joseph F. Poduslo
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Correspondence to Joseph F. Poduslo.

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Wengenack, T., Curran, G. & Poduslo, J. Targeting Alzheimer amyloid plaques in vivo. Nat Biotechnol 18, 868–872 (2000). https://doi.org/10.1038/78482

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