Higuchi Makoto, Iwata Nobuhisa, Matsuba Yukio, Sato Kumi, Sasamoto Kazumi, Saido Takaomi C
Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako-shi, Saitoma 351-0198, Japan.
Nat Neurosci. 2005 Apr;8(4):527-33. doi: 10.1038/nn1422. Epub 2005 Mar 13.
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.
由β-淀粉样肽组成的老年斑的形成是阿尔茨海默病的一个病理标志,在人类大脑中,其形成比疾病发作要早很多年。对这类斑块进行无创检测对于症状前诊断至关重要,并且有助于制定早期预防治疗策略。我们以淀粉样前体蛋白(APP)转基因小鼠作为β-淀粉样蛋白病的模型,在此证明,一种静脉注射的含氟淀粉亲和性化合物可标记脑内斑块,并能通过使用氟-19和氢-1的磁共振成像(MRI)在活体小鼠中使其可视化。我们的研究结果为特异性无创淀粉样成像提供了一个新方向,且不存在辐射暴露风险。这种方法可用于阿尔茨海默病小鼠模型的纵向研究,以寻找与β-淀粉样蛋白病理学相关的生物标志物,以及在使用候选药物治疗后跟踪疾病进程。