title: A longitudinal study of cognition, proton MR spectroscopy and synaptic and neuronal pathology in aging wild-type and AβPPswe-PS1dE9 mice.
abstract: Proton magnetic resonance spectroscopy ((1)H 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 (1)H MRS at 7 Tesla, in the brains of AβPPSswe-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 AβPP-PS1 animals with the hippocampal amyloid-β deposition, TBS-T soluble Aβ levels and high-molecular weight Aβ aggregate levels to gain a better understanding of the possible involvement of Aβ in neurochemical and behavioral changes, cognitive decline and neuropathological features in AβPP-PS1 transgenic mice. Our results show that at 8 months of age AβPPswe-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. AβPP-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 Aβ in inflammatory processes, synaptic dysfunction and impaired neurogenesis.
authors.affiliation: Department of Anatomy, Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Donders Centre for Neuroscience, Nijmegen, The Netherlands.
authors.forename: Diane
authors.initials: D
authors.lastname: Jansen
authors.forename: Valerio
authors.initials: V
authors.lastname: Zerbi
authors.forename: Carola I F
authors.initials: CI
authors.lastname: Janssen
authors.forename: Pieter J W C
authors.initials: PJ
authors.lastname: Dederen
authors.forename: Martina P C
authors.initials: MP
authors.lastname: Mutsaers
authors.forename: Anne
authors.initials: A
authors.lastname: Hafkemeijer
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Janssen
authors.forename: Cindy L M
authors.initials: CL
authors.lastname: Nobelen
authors.forename: Andor
authors.initials: A
authors.lastname: Veltien
authors.forename: Jack J
authors.initials: JJ
authors.lastname: Asten
authors.forename: Arend
authors.initials: A
authors.lastname: Heerschap
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Kiliaan
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D008137:Longitudinal Studies; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D013569:Synapses / Q000378:metabolism / Q000473:pathology*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor