Labeling of Cerebral Amyloid β Deposits In Vivo Using Intranasal Basic Fibroblast Growth Factor and Serum Amyloid P Component in Mice

Journal of Nuclear Medicine

George Perry¹  Marc S. Berridge¹  Joseph C. LaManna¹  Mark A. Smith¹  Sandy L. Siedlak¹  Jiong Shi¹  Gjumrakch Aliev¹  Robert P. Friedland¹ 

关键词: Alzheimer’s disease;    cognitive disorders;    dementia;    amyloid β;    protein;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

There is currently no method for noninvasive imaging of amyloid β (Aβ) deposition in Alzheimer’s disease (AD). Because Aβ plaques are characteristic of AD and Aβ 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 Aβ deposition in a transgenic (Tg) mouse model overexpressing Aβ-protein precursor. Methods: The biodistribution of bFGF injected intranasally was studied using 125I-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 125I-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 Aβ 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 Aβ 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 Aβ plaques. This method may be modified for human studies using intranasal injection of radiolabeled ligands and imaging with SPECT or PET.

【 授权许可】

Unknown