19F and 1H MRI detection of amyloid beta plaques in vivo.
Formation of senile plaques composed of amyloid beta 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 beta amyloidosis, we demonstrate here that an intravenously administered (19)F-containing amyloidophilic compound labels brain plaques and allows them to be visualized in living mice by magnetic resonance imaging (MRI) using (19)F and (1)H. 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 beta pathology as well as to track disease course after treatment with candidate medications.
Higuchi
Makoto
M
Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako-shi, Saitoma 351-0198, Japan. mhiguchi@brain.riken.jp
Iwata
Nobuhisa
N
Matsuba
Yukio
Y
Sato
Kumi
K
Sasamoto
Kazumi
K
Saido
Takaomi C
TC
D000367:Age Factors; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000686:Amyloidosis / Q000175:diagnosis* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D001923:Brain Chemistry / Q000502:physiology; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008559:Memantine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D051379:Mice; D008822:Mice, Transgenic; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging / Q000473:pathology; D011877:Radionuclide Imaging; D013194:Staining and Labeling / Q000379:methods; D013997:Time Factors; D014316:Tritium / Q000493:pharmacokinetics
C114150:1-amino-3-fluoromethyl-5-methyladamantane; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D005456:Fluorescent Dyes; D014316:Tritium; D010751:Phosphopyruvate Hydratase; D008559:Memantine