Neuroscience 2004 Abstract
| Presentation Number: | 224.1 |
|---|---|
| Abstract Title: | MRI approaches for detection of PrP<sup>Sc</sup> in asymptomatic subjects. |
| Authors: |
Sadowski, M.*1
; Wadghiri, Z.4
; Brown, D.5
; Scholtzova, H.1
; Pankiewicz, J.1
; Turnbull, D.3,4
; Wisniewski, T.1,2,3
1Neurol., NYU Sch Med, New York, NY 2Psychiatry, NYU Sch Med, New York, NY 3Pathology, NYU Sch Med, New York, NY 4Radiology, NYU Sch Med, New York, NY 5United Kingdom, 550 First Ave, 10016, |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Neurodegenerative Disorders -- Prion Diseases |
| Session: |
224. Prion Diseases Poster |
| Presentation Time: | Sunday, October 24, 2004 8:00 AM-9:00 AM |
| Location: | San Diego Convention Center - Hall A-H, Board # WW24 |
| Keywords: | prion diseases, PrP protein, lymphoreticular system, imaging |
Prion diseases are a group of invariably fatal neurodegenerative diseases associated with the conformational transformation of prion protein PrPC (C-cellular) into a toxic and infectious conformer PrPSc (Sc-scrapie). PrPSc accumulates in organs which express PrPC, using PrPC as a template for its own replication. Carriers of prion infections harbor PrPSc in the lymphatic organs for months and years before the disease involves their brains and first neurological symptoms occur. Asymptomatic carriers constitute a reservoir for further spread of infection to other humans through organ transplantation and blood transfusion. Currently, no test which identifies asymptomatic carries of prion infection exists. Therefore, we have developed a novel MRI approach to visualize the presence of PrPSc in lymphatic organs. Several synthetic, non-toxic peptides that have high binding affinity to PrPSc were developed using a pepscan approach. PrP145-174 which had the highest binding affinity was synthesized with DTPA on its N-terminus. Gadolinium (Gd) was chelated to DTPA-PrP145-174. Gd-DTPA-PrP145-174 or DTPA-PrP145-174 were administered intravenously into pre-symptomatic CD-1 mice infected with 139A or ME7 scrapie strains and into non-infected CD-1 mice. Animals were sacrificed 6 hours later and 7-Tesla μMRI of the spleen was performed (TE/TR/FA=5-ms/50-ms/20O). In the spleens of infected mice, but not in controls a significant change in T2 signal intensity following Gd-DTPA-PrP145-174 administration was found. The susceptibility effect induced by the Gd altered the spleen's white pulp predominantly, which is known to specifically accumulate PrPSc. This study demonstrates that PrPSc specific Gd-tagged-ligands, can be used for the MRI identification of pre-symptomatic prion infection carriers in model animals.
Supported by NIH grants AG20747, AG20245, NS47433
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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