Salas, IH;
Weerasekera, A;
Ahmed, T;
Callaerts-Vegh, Z;
Himmelreich, U;
D'Hooge, R;
Balschun, D;
... De Strooper, B; + view all
(2018)
High fat diet treatment impairs hippocampal long-term potentiation without alterations of the core neuropathological features of Alzheimer disease.
Neurobiology of Disease
, 113
pp. 82-96.
10.1016/j.nbd.2018.02.001.
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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.
Type: | Article |
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Title: | High fat diet treatment impairs hippocampal long-term potentiation without alterations of the core neuropathological features of Alzheimer disease |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1016/j.nbd.2018.02.001 |
Publisher version: | http://doi.org/10.1016/j.nbd.2018.02.001 |
Language: | English |
Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
Keywords: | Alzheimer disease; Type 2 diabetes; Metabolic stress; Behavior; Electrophysiology; Magnetic resonance spectroscopy |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UK Dementia Research Institute HQ |
URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10043147 |
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