Manganese Enhanced MRI of APP-induced neurodegeneration and recovery in an olfactory-based AD model

Thursday, October 11, 2012 — Poster Session III
10:00 a.m. – Noon	Natcher Conference Center, Building 45	NINDS	IMAG-26

* FARE Award Winner

Authors

• G. Saar
• N. Cheng
• A.P. Koretsky
• L. Belluscio

Abstract

Olfactory dysfunction is an early symptom of Alzheimer’s disease (AD), suggesting that olfactory sensory neurons (OSNs) are sensitive to AD related factors. A reversible olfactory-based AD model, which recently established that degeneration of OSNs can be rapidly induced by overexpressing amyloid precursor protein (APP), was used to follow progression of neural pathology and its recovery, in vivo, using MRI. MEMRI can detect layers in different areas of the brain, including olfactory bulb (OB), and highlight discrete anatomical features such as glomeruli in OB. Since OSNs regenerate continuously and project their axons directly to OB glomeruli, we performed MEMRI in both control and mutant mice to detect degeneration and recovery of OSNs. The OB volumes of 3-4 week old mutant mice decreased by ~50% compared to controls. OB shape and structure was altered with the glomerular layer virtually eliminated. After APP expression was turned off using doxcycline, we observed a striking recovery of OB layers, and reappearance of the glomerular layer. This study demonstrates that MEMRI can detect anatomical changes associated with both APP-induced neurodegeneration and recovery in the OB. Ultimately we believe that MEMRI can serve as a unique in vivo screening tool to identify potential therapeutics and their efficacy.

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