Neuroscience 2002 Abstract
| Presentation Number: | 228.8 |
|---|---|
| Abstract Title: | MOLECULAR TARGETING OF ALZHEIMER'S AMYLOID PLAQUES FOR CONTRAST-ENHANCED MAGNETIC RESONANCE IMAGING. |
| Authors: |
Wengenack, T. M.*1
; Curran, G. L.1
; Wisniewski, T.2
; Sigurdsson, E. M.2
; Macura, S. I.1
; Borowski, B. J.1
; Jack, Jr. , C. R.1
; Poduslo, J. F.1
1Neurology, Mayo Clinic, Rochester, MN 2NYU, NY, NY |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Neurodegenerative Disorders -- Alzheimers Disease: Other |
| Secondary Theme and Topics | Techniques in Neuroscience<br />- Staining, tracing and imaging techniques |
| Session: |
228. Neurodegenerative disorders: Alzheimer's disease--imaging studies Slide |
| Presentation Time: | Monday, November 4, 2002 9:45 AM-10:00 AM |
| Location: | Room 315A |
| Keywords: | Blood-brain barrier, Beta amyloid, Diagnosis, Transgenic mouse |
Smart molecular probes for both diagnostic and therapeutic purposes are expected to provide quantum advances in clinical medicine and biomedical research. We describe such a probe that targets β-amyloid plaques of Alzheimer’s disease and is detectable by magnetic resonance imaging (MRI) because of contrast imparted by gadolinium labeling. Three essential properties are shown to exist in this smart molecular probe, putrescine-gadolinium-amyloid-β peptide: 1) transport across the blood-brain-barrier following intravenous injection which is conferred by the polyamine moiety, 2) binding to plaques with high affinity by the putrescine-labeled amyloid-β peptide, and 3) MRI detectability conferred by the contrast agent, gadolinium. MRI was performed on ex vivo tissue specimens at a spatial resolution approximating plaque size (62.5 μm3), in order to prove the concept that the probe can selectively enhance plaques when administered intravenously. The plaque-to-background tissue contrast-to-noise ratio, that was precisely correlated with histologically stained plaques, was enhanced more than 9-fold in all regions of cortex and hippocampus following intravenous administration of this probe in AD transgenic mice. A major engineering effort to improving spatial resolution is underway in clinical MRI, which may enable in vivo imaging at the resolution of individual plaques with this or similar contrast probes. This will enable early diagnosis and also provide a direct measure of the efficacy of anti-amyloid therapies currently being developed.
Supported by Alzheimer's Association; NIA AG16574, AG11378, AG17617; Mayo Foundation
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2002 Neuroscience Meeting Planner. Orlando, FL: Society for Neuroscience, 2002. Online.
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