Labeling of cerebral amyloid beta deposits in vivo using intranasal basic fibroblast growth factor and serum amyloid P component in mice.
Labeling of cerebral amyloid beta deposits in vivo using intranasal basic fibroblast growth factor and serum amyloid P component in mice.
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发表时间：
2002-08
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通讯作者：
Jiong Shi;George Perry;M. Berridge;G. Aliev;S. Siedlak;Mark A. Smith;J. LaManna;R. Friedland
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作者：
Jiong Shi;George Perry;M. Berridge;G. Aliev;S. Siedlak;Mark A. Smith;J. LaManna;R. Friedland
目前还没有方法对阿尔茨海默病（AD）中β淀粉样蛋白（Abeta）沉积进行无创成像。由于Abeta斑块是AD的特征，并且Abeta沉积物含有丰富的硫酸肝素蛋白聚糖，可以结合碱性成纤维细胞生长因子（bFGF）和血清淀粉样蛋白P成分（SAP），因此我们研究了一种新的配体递送途径，以评估Abeta在过表达Abeta蛋白前体的转基因（Tg）小鼠模型中的沉积。方法采用（125）I-bFGF在Tg和野生型对照小鼠鼻内注射bFGF，光镜和电镜下采用未标记bFGF和SAP免疫细胞化学方法观察bFGF的生物分布。结果Tg小鼠脑组织中（125）I-bFGF含量比野生型小鼠高3 ~ 5倍（P < 0.05）。在Tg小鼠的皮层和微血管中鼻内给予bFGF或SAP标记的大脑β斑块，而在野生型小鼠中则没有。未鼻内注射配体的Tg小鼠bFGF染色较弱，未见SAP染色。在Tg小鼠中，bFGF和SAP染色了Abeta沉积物边缘周围和整个皮层的神经元。未鼻注bFGF的Tg小鼠神经元仅呈弱染色，未鼻注SAP的Tg小鼠SAP未见染色，野生型对照小鼠bFGF和SAP均未见染色。结论：我们报告了一种新的无创标记β斑块的方法。这种方法可以用于人体研究，使用鼻内注射放射性标记配体和SPECT或PET成像。
UNLABELLED There is currently no method for noninvasive imaging of amyloid beta (Abeta) deposition in Alzheimer's disease (AD). Because Abeta plaques are characteristic of AD and Abeta deposits contain abundant heparan sulfate proteoglycans that can bind basic fibroblast growth factor (bFGF) and serum amyloid P component (SAP), we investigated a novel route of ligand delivery to the brain to assess Abeta deposition in a transgenic (Tg) mouse model overexpressing Abeta-protein precursor. METHODS The biodistribution of bFGF injected intranasally was studied using (125)I-bFGF in Tg and wild-type control mice and by unlabeled bFGF and SAP immunocytochemistry with light and electron microscopy. RESULTS Three- to 5-fold higher amounts of (125)I-bFGF were found in the brain of Tg mice than that of wild-type mice (P < 0.05). bFGF or SAP given intranasally labeled cerebral Abeta plaques in the cortex and microvessels of Tg mice but not in wild-type mice. Weak bFGF staining and no SAP staining were detected in Tg mice without intranasal injection of the ligands. bFGF and SAP stained neurons around the rim of Abeta deposits and throughout the cortex in Tg mice. There was only weak staining of neurons in Tg mice without intranasal injection of bFGF and no staining of SAP in Tg mice without intranasal injection of SAP. No bFGF or SAP staining was evident in wild-type control mice. CONCLUSION We report a novel noninvasive method for labeling Abeta plaques. This method may be modified for human studies using intranasal injection of radiolabeled ligands and imaging with SPECT or PET.