A Longitudinal Study of Cognition, Proton MR Spectroscopy and Synaptic and Neuronal Pathology in Aging Wild type and AbPPswe PS1dE9 Mice
Proton magnetic resonance spectroscopy (1H MRS) is a valuable tool in Alzheimer's disease research, investigating the functional integrity of the brain. The present longitudinal study set out to characterize the neurochemical profile of the hippocampus, measured by single voxel 1H MRS at 7 Tesla, in the brains of AbPPSswe PS1dE9 and wild type mice at 8 and 12 months of age. Furthermore, we wanted to determine whether alterations in hippocampal metabolite levels coincided with behavioral changes, cognitive decline and neuropathological features, to gain a better understanding of the underlying neurodegenerative processes. Moreover, correlation analyses were performed in the 12 month old AbPP PS1 animals with the hippocampal amyloid b deposition, TBS T soluble Ab levels and high molecular weight Ab aggregate levels to gain a better understanding of the possible involvement of Ab in neurochemical and behavioral changes, cognitive decline and neuropathological features in AbPP PS1 transgenic mice. Our results show that at 8 months of age AbPPswe PS1dE9 mice display behavioral and cognitive changes compared to age matched wild type mice, as determined in the open field and the (reverse) Morris water maze. However, there were no variations in hippocampal metabolite levels at this age. AbPP PS1 mice at 12 months of age display more severe behavioral and cognitive impairment, which coincided with alterations in hippocampal metabolite levels that suggest reduced neuronal integrity. Furthermore, correlation analyses suggest a possible role of Ab in inflammatory processes, synaptic dysfunction and impaired neurogenesis.
PloS one