Neuroscience 2004 Abstract
Presentation Number: | 789.3 |
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Abstract Title: | Time course and dose response of 125-i Gd[N-4ab/Q-4ab] Aβ30 binding to Alzheimer plaques of APP, PS1 transgenic mice <I>in vivo.</I> |
Authors: |
Wengenack, T. M.*1
; Holacek, S. S.1
; Curran, G. L.1
; Kandimalla, K. K.1
; Gregor, D. M.1
; Poduslo, J. F.1
1Dept. Neurol., Mayo Col. of Med., Rochester, MN |
Primary Theme and Topics |
Neurological and Psychiatric Conditions - Neurodegenerative Disorders -- Alzheimer's Disease: Experimental models |
Session: |
789. Amyloid Plaques and Associated Pathologies Poster |
Presentation Time: | Tuesday, October 26, 2004 3:00 PM-4:00 PM |
Location: | San Diego Convention Center - Hall A-H, Board # UU1 |
Keywords: | Alzheimer's disease, imaging, MRI, autoradiography |
Putative therapeutic agents to treat Alzheimer’s disease (AD) will require validation in the clinic. All diagnostic imaging techniques would benefit, if not require a plaque/tangle specific probe to not only definitively diagnose AD, but also monitor the efficacy of those therapeutic agents. Magnetic resonance imaging (MRI) is the only imaging technique with resolution high enough to potentially image individual plaques. We have previously reported that radiolabeled polyamine modified Aβ40 with increased BBB permeability not only labels plaques in vivo in APP, PS1 transgenic mice, but that the gadolinium (Gd) labeled form of the peptide produces plaque selective contrast enhancement on T1-weighted MRI in ex vivo brains following IV injection. We have developed a second generation, totally synthetic peptide, Gd[N-4ab/Q-4ab] Aβ30. The purpose of the present study was to optimize time of injection and dose of Gd[N-4ab/Q-4ab] Aβ30 using 125-I radiolabeled peptide and autoradiographic techniques. APP, PS1 transgenic mice (8 mo.) were injected IV with equal amounts (500 µg) of 125-I Gd[N-4ab/Q-4ab] Aβ30 and then perfused/fixed after 1, 2, 4, or 8 hrs., or injected IV with 0.31, 0.63, 1.25, or 2.50 mg of peptide and perfused/fixed after 2 hrs. Brains were frozen in chilled isopentane and sections (15 µm) cut with a cryostat. After immunohistochemistry for Aβ, sections were dipped in autoradiographic emulsion and exposed up to 8 weeks. Silver grains were counted over plaques and parenchyma using stereological methods and corrected for background. Highest densities of silver grains were counted over plaques at 1 and 2 hrs post injection while the highest density in the parenchyma was at 1 hr, indicating that a post injection duration of 2 hrs should provide maximal plaque to parenchyma contrast in MRI. (Support provided by NIH (AG22034).).
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2004 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2004. Online.
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