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Spatial reversal learning defect coincides with hypersynchronous telencephalic BOLD functional connectivity in $APP^{NL-F/NL-F}$ knock-in mice

Journal Contribution - e-publication

Amyloid pathology occurs early in Alzheimer's disease (AD), and has therefore been the focus of numerous studies. Transgenic mouse models have been instrumental to study amyloidosis, but observations might have been confounded by APP-overexpression artifacts. The current study investigated early functional defects in an APP knock-in mouse model, which allows assessing the effects of pathological amyloid-beta (A beta) without interference of APP-artifacts. Female APP(NL/NL) knock-in mice of 3 and 7 months old were compared to age-matched APP(NL-F/NL-F) mice with increased A beta 42/40 ratio and initial A beta-plaque deposition around 6 months of age. Spatial learning was examined using a Morris water maze protocol consisting of acquisition and reversal trials interleaved with reference memory tests. Functional connectivity (FC) of brain networks was assessed using restingstate functional MRI (rsfMRI). The Morris water maze data revealed that 3 months old APP(NL-F/NL-F) mice were unable to reach the same reference memory proficiency as APP(NL/NL) mice after reversal training. This cognitive defect in 3-month-old APP(NL-F/NL-F) mice coincided with hypersynchronous FC of the hippocampal, cingulate, caudate-putamen, and default-mode-like networks. The occurrence of these defects in APP(NL-F/NL-F) mice demonstrates that cognitive flexibility and synchronicity of telencephalic activity are specifically altered by early A beta pathology without changes in APP neurochemistry.
Journal: Scientific Reports
Volume: 8
Number of pages: 11
Publication year:2018
Keywords:Multidisciplinary sciences
CSS-citation score:1
Authors from:Higher Education