Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Neurobiology of disease, 2018-05, Vol.113, p.82-96

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• 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. •High fat diet could not trigger Alzheimer’s Disease (AD) pathology in a knock-in mouse model.•High fat diet exposure did not affect amyloid beta production, Tau phosphorylation, or cognitive performance.•Long term diet treatment triggers a decrease of N-acetyl aspartate/myo-inositol metabolite ratios in the hippocampus.•Impaired long term potentiation is seen in hippocampal acute slices after 10 months of high fat diet exposure.•No alterations in hippocampal insulin response or insulin signaling is observed in high fat diet-treated mice.