Quantitative in vivo measurement of early axonal transport deficits in a triple transgenic mouse model of Alzheimer's disease using manganese-enhanced MRI

Impaired axonal transport has been linked to the pathogenic processes of Alzheimer's disease (AD) in which axonal swelling and degeneration are prevalent. The development of non-invasive neuroimaging methods to quantitatively assess in vivo axonal transport deficits would be enormously valuable...

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Bibliographic Details
Published in:NeuroImage (Orlando, Fla.) Fla.), 2011-06, Vol.56 (3), p.1286-1292
Main Authors: Kim, Jieun, Choi, In-Young, Michaelis, Mary L., Lee, Phil
Format: Article
Language:English
Subjects:
Aging - physiology
Alzheimer Disease - pathology
Alzheimer Disease - physiopathology
Alzheimer's disease
Amyloid beta-Protein Precursor - genetics
Animals
Axonal transport
Axonal Transport - physiology
Brain - pathology
Brain - physiopathology
Chlorides - pharmacokinetics
Cytoskeleton
Data Interpretation, Statistical
Echo-Planar Imaging
Humans
Magnetic Resonance Imaging
Manganese Compounds - pharmacokinetics
MEMRI
Mice
Mice, Transgenic
Mutation
NMR
Nuclear magnetic resonance
Olfactory Pathways - cytology
Olfactory Pathways - physiopathology
Phosphorylation
Presenilin-1 - genetics
Rodents
Studies
Synapses - physiology
T1 mapping
tau Proteins - genetics
Triple transgenic mouse model
Turbinates - metabolism
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Summary:Impaired axonal transport has been linked to the pathogenic processes of Alzheimer's disease (AD) in which axonal swelling and degeneration are prevalent. The development of non-invasive neuroimaging methods to quantitatively assess in vivo axonal transport deficits would be enormously valuable to visualize early, yet subtle, changes in the AD brain, to monitor the disease progression and to quantify the effect of drug intervention. A triple transgenic mouse model of AD closely resembles human AD neuropathology. In this study, we investigated age-dependent alterations of the axonal transport rate in the triple transgenic mouse olfactory system, using fast multi-sliced T1 mapping with manganese-enhanced MRI. The data show that impairment in axonal transport is a very early event in AD pathology in these mice, preceding both deposition of Aβ plaques and formation of Tau fibrils. ► Axonal transport impairment precedes extracellular Aβ and Tau pathologies in 3×Tg-AD mice. ► Quantitative T1 mapping MEMRI with the use of significantly lower MnCl2 dose. ► Quantitative measurement of axonal transport rates in the living mouse brain.
ISSN:1053-8119
1095-9572
DOI:10.1016/j.neuroimage.2011.02.039