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19F and 1H MRI detection of amyloid β plaques in vivo

Nature Neuroscience volume 8, pages 527–533 (2005)Cite this article

Abstract

Formation of senile plaques composed of amyloid β peptide, a pathological hallmark of Alzheimer disease, in human brains precedes disease onset by many years. Noninvasive detection of such plaques could be critical in presymptomatic diagnosis and could contribute to early preventive treatment strategies. Using amyloid precursor protein (APP) transgenic mice as a model of amyloid β amyloidosis, we demonstrate here that an intravenously administered 19F-containing amyloidophilic compound labels brain plaques and allows them to be visualized in living mice by magnetic resonance imaging (MRI) using 19F and 1H. Our findings provide a new direction for specific noninvasive amyloid imaging without the danger of exposure to radiation. This approach could be used in longitudinal studies in mouse models of Alzheimer disease to search for biomarkers associated with amyloid β pathology as well as to track disease course after treatment with candidate medications.

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Figure 1: Amyloid plaques stained with FSB.
Figure 2: 3D RARE 19F MRI and increased signal intensity in T1-weighted gradient-echo 1H magnetic resonance by stereotaxic injection of FSB into the bilateral basal ganglia of 6-month-old wild-type mice.
Figure 3: Examination of potential toxicity of FSB.
Figure 4: Detection of amyloid plaques (indicated by arrows and arrowheads) in the brain of a 20-month-old Tg2576 mouse by MRI with intravenous injection of FSB.
Figure 5: Contrast enhancement of 1H MRI of hippocampal senile plaques in Tg2576 mice in 1H MRI after intravenous FSB administration (left, 16-month-old; right, 23-month-old).
Figure 6: Quantification of 19F- and 1H MRI using APP transgenic mice carrying different amyloid β burdens.

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Acknowledgements

We thank M. Sekiguchi for technical assistance; K H. Ashe, University of Minnesota, for providing Tg2576; C. Itakura and K. Tanaka, RIKEN Brain Science Institute, for administrative support; and T. Iwatsubo, University of Tokyo, for helpful advice. This research was supported by research grants from the RIKEN Brain Science Institute and from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako-shi, Saitoma, 351-0198, Japan

    Makoto Higuchi, Nobuhisa Iwata, Yukio Matsuba & Takaomi C Saido

  2. Dojin Laboratories, Mashiki-machi, Kumamoto, 861-2202, Japan

    Kumi Sato & Kazumi Sasamoto

Authors
  1. Makoto Higuchi
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  2. Nobuhisa Iwata
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  4. Kumi Sato
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Correspondence to Makoto Higuchi or Takaomi C Saido.

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Supplementary information

Supplementary Fig. 1

In vivo 3D RARE 19F magnetic resonance image of a 20-month-old transgenic mouse brain; 60-min scan. (PDF 35 kb)

Supplementary Fig. 2

Magnetic resonance detection of aging-dependent amyloid β deposition in APP transgenic mice. (PDF 59 kb)

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Higuchi, M., Iwata, N., Matsuba, Y. et al. 19F and 1H MRI detection of amyloid β plaques in vivo. Nat Neurosci 8, 527–533 (2005). https://doi.org/10.1038/nn1422

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