Quantitative evaluation of MRI and histological characteristics of the 5xFAD Alzheimer mouse brain

Assessment of beta-amyloid (A beta) plaque load in Alzheimer's disease by MRI would provide an important biomarker to monitor disease progression or treatment response. Alterations in tissue structure caused by the presence of A beta may cause localised changes that can be detected by quantitative T-1 and T-2 relaxation time measurements averaged over larger areas of tissue than that of individual plaques. We constructed depth profiles of the T-1 and T-2 relaxation times of the cerebral cortex with subjacent white matter and hippocampus in six 5xFAD transgenic and six control mice at 11 months of age. We registered these profiles with corresponding profiles of three immunohistochemical markers: beta-amyloid; neuron-specific nuclear protein (NeuN), a marker of neuronal cell load; and myelin basic protein (MBP), a marker of myelin load. We found lower T-1 in the 5xFAD transgenic mice compared to wild type control mice at all depths, with maximum sensitivity for detection at specific layers. T1 negatively correlated with A beta staining intensity in the 5xFAD mice which had no changes in NeuN and MBP staining compared to wild type mice. We postulate that these relaxation time changes are due to the presence of beta-amyloid in the transgenic mice. It may be clinically feasible to develop a similar layered analysis protocol as a biomarker for Alzheimer's disease in humans. (C) 2013 Elsevier Inc. All rights reserved.