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Neural oscillations during cognitive processes in an App knock-in mouse model of Alzheimer's disease pathology

Jacob, S., Davies, G., De Bock, M., Hermans, B., Wintmolders, C., Bottelbergs, A., Borgers, M., Theunis, C., Van Broeck, B., Manyakov, N. V., Balschun, D. & Drinkenburg, W. H. I. M., 8-Nov-2019, In : Scientific Reports. 9, 19 p., 16363.

Research output: Contribution to journalArticleAcademicpeer-review

  • Sofia Jacob
  • Gethin Davies
  • Marijke De Bock
  • Bart Hermans
  • Cindy Wintmolders
  • Astrid Bottelbergs
  • Marianne Borgers
  • Clara Theunis
  • Bianca Van Broeck
  • Nikolay V. Manyakov
  • Detlef Balschun
  • Wilhelmus H. I. M. Drinkenburg

Multiple animal models have been created to gain insight into Alzheimer's disease (AD) pathology. Among the most commonly used models are transgenic mice overexpressing human amyloid precursor protein (APP) with mutations linked to familial AD, resulting in the formation of amyloid beta plaques, one of the pathological hallmarks observed in AD patients. However, recent evidence suggests that the overexpression of APP by itself can confound some of the reported observations. Therefore, we investigated in the present study the App(NL-G-F)model, an App knock-in (App-KI) mouse model that develops amyloidosis in the absence of APP-overexpression. Our findings at the behavioral, electrophysiological, and histopathological level confirmed an age-dependent increase in A beta 1-42 levels and plaque deposition in these mice in accordance with previous reports. This had apparently no consequences on cognitive performance in a visual discrimination (VD) task, which was largely unaffected in App(NL-G-F) mice at the ages tested. Additionally, we investigated neurophysiological functioning of several brain areas by phase-amplitude coupling (PAC) analysis, a measure associated with adequate cognitive functioning, during the VD task (starting at 4.5 months) and the exploration of home environment (at 5 and 8 months of age). While we did not detect age-dependent changes in PAC during home environment exploration for both the wild-type and the App(NL-G-F) mice, we did observe subtle changes in PAC in the wild-type mice that were not present in the App(NL-G-F) mice.

Original languageEnglish
Article number16363
Number of pages19
JournalScientific Reports
Volume9
Publication statusPublished - 8-Nov-2019

    Keywords

  • GAMMA OSCILLATIONS, EPILEPTIFORM ACTIVITY, NETWORK OSCILLATIONS, THETA, FREQUENCY, MEMORY, INFORMATION, DYSFUNCTION, SEIZURES, EEG

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