Evolution of beta-amyloid induced neuropathology: magnetic resonance imaging and anatomical comparisons in the rodent...

Alzheimer's disease (AD) is characterized by the anatomical appearance of beta-amyloid (betaA) plaques and neurofibrillary tangles. These changes are also associated with cyclical inflammation, oxidative damage and, as inferred from the autopsied brains of patients, progressive injury to neurons. Here, we report the short-term effects of an intrahippocampal injection of the toxic betaA peptide fragment 25-35 in rats using quantitative magnetic resonance imaging (MRI) methods. Physiological changes within the cornu ammonis 1 (CA1) region of the hippocampus were monitored using a 1.5 T scanner at time points of 0.25, 1 and 24 h, and 7 and 14 days post injection. Spin echo T2-weighted (T2W) and diffusion weighted (DW) images were sequentially acquired. Apparent diffusion coefficients (ADC) were calculated and compared with histological alterations. A significant elevation in mean ADC values (17%) was observed in the ipsilateral CA1 at 14 days. The ADC changes were associated with disrupted pyramidal cells and nuclear lysis observed in histological sections. The contralateral CA1 exhibited a significant decrease in mean ADC of 15% at 14 days post treatment. Histological changes in the contralateral hippocampus suggested decreased neuronal density. T2W maps revealed no significant differences between the active betaA 25-35 fragment and its non-active analog, betaA 35-25. In conclusion, these results, based on changes in hippocampal ADC, demonstrate that the betaA 25-35 treatment induced pathology consistent with edema and cellular necrosis. This is the first report describing the evolution of AD-like pathology in an animal model using DW imaging.