title: Laminar specific detection of APP induced neurodegeneration and recovery using MEMRI in an olfactory based Alzheimer's disease mouse model.
abstract: Manganese enhanced MRI (MEMRI) was used to detect specific laminar changes in the olfactory bulb (OB) to follow the progression of amyloid precursor protein (APP)-induced neuronal pathology and its recovery in a reversible olfactory based Alzheimer's disease (AD) mouse model. Olfactory dysfunction is an early symptom of AD, which suggests that olfactory sensory neurons (OSNs) may be more sensitive to AD related factors than neurons in other brain areas. Previously a transgenic mouse model was established that causes degeneration of OSNs by overexpressing humanized APP (hAPP), which results in a disruption of the olfactory circuitry with changes in the glomerular structure. In the present work, OB volume and manganese enhancement of the glomerular layer in the OB were decreased in mutant mice. Turning off APP overexpression with doxycycline produced a significant increase in manganese enhancement of the glomerular layer after only 1week, and further recovery after 3weeks, while treatment with Aβ antibody produced modest improvement with MRI measurements. Thus, MEMRI enables a direct tracking of laminar specific neurodegeneration through a non-invasive in vivo measurement. The use of MRI will enable assessment of the ability of different pharmacological reagents to block olfactory neuronal loss and can serve as a unique in vivo screening tool to both identify potential therapeutics and test their efficacy.
authors.affiliation: Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: saarg@mail.nih.gov.
authors.forename: Galit
authors.initials: G
authors.lastname: Saar
authors.affiliation: Developmental Neuronal Plasticity Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA; Alberta Children's Hospital Research Institute (ACHRI), Cumming School of Medicine University of Calgary, Calgary, AB T2N 4N1, Canada. Electronic address: ncheng@ucalgary.ca.
authors.forename: Ning
authors.initials: N
authors.lastname: Cheng
authors.affiliation: Developmental Neuronal Plasticity Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: belluscl@mail.nih.gov.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Belluscio
authors.affiliation: Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: koretskya@ninds.nih.gov.
authors.forename: Alan P
authors.initials: AP
authors.lastname: Koretsky
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D003287:Contrast Media; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008345:Manganese; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009830:Olfactory Bulb / Q000378:metabolism / Q000473:pathology*
chemical_list: D016564:Amyloid beta-Protein Precursor; D003287:Contrast Media; D008345:Manganese
keywords: Alzheimer's disease; Manganese enhanced MRI; Molecular imaging; Olfaction