A longitudinal study of cognition, proton MR spectroscopy and synaptic and neuronal pathology in aging wild-type and A beta PPswe-PS1dE9 mice

Abstract

Proton magnetic resonance spectroscopy (H-1 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 H-1 MRS at 7 Tesla, in the brains of A beta PPSswe-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 A beta PP-PS1 animals with the hippocampal amyloid-beta deposition, TBS-T soluble A beta levels and high-molecular weight A beta aggregate levels to gain a better understanding of the possible involvement of A beta in neurochemical and behavioral changes, cognitive decline and neuropathological features in A beta PP-PS1 transgenic mice. Our results show that at 8 months of age A beta PPswe-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. A beta PP-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 A beta in inflammatory processes, synaptic dysfunction and impaired neurogenesis.