期刊
NEUROBIOLOGY OF DISEASE
卷 113, 期 -, 页码 82-96出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2018.02.001
关键词
Alzheimer disease; Type 2 diabetes; Metabolic stress; Behavior; Electrophysiology; Magnetic resonance spectroscopy
资金
- Fonds voor Wetenschappelijk Onderzoek (FWO)
- KU Leuven
- VIB, IUAP a Methusalem grant of the KU Leuven/Flemish Government [P7/16]
- stichting Alzheimer Onderzoek (SAO-Belgium)
- Bax-Vanluffelen Chair for Alzheimer's Disease and Opening the Future
- Vlaams Initiatief voor Netwerken voor Dementie Onderzoek (VIND, Strategic Basic Research Grant) [135043]
- UK-DRI
- MRC
- Alzheimer society UK
- Alzheimer Research UK
- Innovation Ingenio-Consolider grant [CSD2010-00045]
- Spanish Ministry of Science [SAF2010-14906]
- Spanish Ministry of Economy and Competitiveness [SAF2013-45392, SAF2016-76722]
- EC-FP7-MC-ITN Transact [316679]
- Medical Research Council [MC_PC_17116] Funding Source: researchfish
- MRC [MC_PC_17116] Funding Source: UKRI
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/myoinositol 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.
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