High fat diet treatment impairs hippocampal long-term potentiation without alterations of the core neuropathological features of Alzheimer disease

Isabel H. Salas, Akila Weerasekera, Tariq Ahmed, Zsuzsanna Callaerts-Vegh, Uwe Himmelreich, Rudi D'Hooge, Detlef Balschun, Takaomi C. Saido, Bart De Strooper, Carlos G. Dotti

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7 Citations (Scopus)

Abstract

Type 2 diabetes (T2DM) and obesity might increase the risk for AD by 2-fold. Different attempts to model the effect of diet-induced diabetes on AD pathology in transgenic animal models, resulted in opposite conclusions. Here, we used a novel knock-in mouse model for AD, which, differently from other models, does not overexpress any proteins. Long-term high fat diet treatment triggers a reduction in hippocampal N-acetyl-aspartate/myo-inositol metabolites ratio and impairs long term potentiation in hippocampal acute slices. Interestingly, these alterations do not correlate with changes in the core neuropathological features of AD, i.e. amyloidosis and Tau hyperphosphorylation. The data suggest that AD phenotypes associated with high fat diet treatment seen in other models for AD might be exacerbated because of the overexpressing systems used to study the effects of familial AD mutations. Our work supports the increasing insight that knock-in mice might be more relevant models to study the link between metabolic disorders and AD.

Original languageEnglish
Pages (from-to)82-96
Number of pages15
JournalNeurobiology of Disease
Volume113
DOIs
Publication statusPublished - May 2018

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Keywords

  • Alzheimer disease
  • Behavior
  • Electrophysiology
  • Magnetic resonance spectroscopy
  • Metabolic stress
  • Type 2 diabetes

ASJC Scopus subject areas

  • Neurology

Cite this

Salas, I. H., Weerasekera, A., Ahmed, T., Callaerts-Vegh, Z., Himmelreich, U., D'Hooge, R., Balschun, D., Saido, T. C., De Strooper, B., & Dotti, C. G. (2018). High fat diet treatment impairs hippocampal long-term potentiation without alterations of the core neuropathological features of Alzheimer disease. Neurobiology of Disease, 113, 82-96. https://doi.org/10.1016/j.nbd.2018.02.001