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IC‐P‐029: Magnetic resonance imaging of APP/PS1/Tau mice on gradated iron diets
Author(s) -
Meadowcroft Mark D.,
Peters Douglas G.,
Haaf Michael P.,
Yang Qing X.,
Connor James R.
Publication year - 2015
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2015.06.049
Subject(s) - tangle , genetically modified mouse , magnetic resonance imaging , chemistry , biomarker , in vivo , amyloid (mycology) , neurotoxicity , pathology , neuroscience , transgene , psychology , nuclear magnetic resonance , biochemistry , medicine , biology , radiology , toxicity , physics , gene , genetics , mathematics , pure mathematics
Background: There is converging evidence that iron overload is involved in both amyloid-beta (Ab) plaque and neurofibrillary tangle (NFT) formation. Our previous results have demonstrated that hypo-intensities on T2and T2*-weighted MRI datasets coincide with Ab plaques in AD and transgenic neural tissue. There are crucial unanswered questions in the current literature on how iron and amyloid fibrils are involved in plaque and tangle genesis in the living brain and the neurotoxic impact of amyloidogenesis. We hypothesize that iron is a cofactor in the genesis of Ab plaques and plays a synergistic function in relation to Ab plaque neurotoxicity. The goal of this research is to 1) determine the in vivo relationship between iron and AD pathology, 2) observe the effects of different iron diets on spatial and learning memory using escape maze tasks, and 3) establish the cyto-architectural basis of AD pathology in relation to MR metrics. Methods: Four groups of six APP/PS1/ Tau transgenic mice were randomized into four diet groups consisting of Fe deficient, 35 mg/kg Fe, 200 mg/kg Fe, and 0.1% lipophilic iron. Mice were scanned on a 7.0 T system at baseline and at three month increments for one year along with cognitive and blood biomarker measures. Group based parametric map analysis and region of interest (ROI) based transverse relaxation metrics were generated. Results: Group based transverse parameter maps and ROI analysis of mice fed the iron diets demonstrate that mice have shorter transverse relaxation in a gradated step-wise fashion with increasing iron diet in the same cortical regions. Conclusions: The parametric group analysis and segmentation changes confirm that high iron diets significantly alter the APP/PS1/Tau brain. Our previous data has shown that transverse relaxation is a measure of plaque formation and iron loading; as such, the cortical relaxation changes are hypothesized to reflect an accumulation of iron and Ab plaques genesis in the cortex. This research will generate new information for understanding the role of homeostatic iron overload in Ab plaque and NFT formation within the AD brain to determine how iron levels affect plaque morphology, pTau formation, iron management, inflammatory response, and cognition. P1-163 MANGANESE-ENHANCED MAGNETIC RESONANCE IMAGING (MEMRI) MEASURES PRE-PATHOLOGICAL NEURONAL DYSFUNCTION BEFORE THE APPEARANCE OF TAU PATHOLOGY IN RTG4510 MICE