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

¹ Department of Neurology, Case Western Reserve University, University Hospitals of Cleveland, Cleveland, Ohio
² Department of Pathology, Case Western Reserve University, University Hospitals of Cleveland, Cleveland, Ohio
³ Department of Radiology, Case Western Reserve University, University Hospitals of Cleveland, Cleveland, Ohio
⁴ Department of Anatomy, Case Western Reserve University, University Hospitals of Cleveland, Cleveland, Ohio

There is currently no method for noninvasive imaging of amyloid ß (Aß) deposition in Alzheimer’s disease (AD). Because Aß plaques are characteristic of AD and Aß 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 Aß deposition in a transgenic (Tg) mouse model overexpressing Aß-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 Aß 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 Aß 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 Aß plaques. This method may be modified for human studies using intranasal injection of radiolabeled ligands and imaging with SPECT or PET.

Key Words: Alzheimer’s disease • cognitive disorders • dementia • amyloid ß • protein

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