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 language | English |
|---|---|
| Pages (from-to) | 82-96 |
| Number of pages | 15 |
| Journal | Neurobiology of Disease |
| Volume | 113 |
| DOIs | |
| Publication status | Published - 1 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
High fat diet treatment impairs hippocampal long-term potentiation without alterations of the core neuropathological features of Alzheimer disease. / 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.
In: Neurobiology of Disease, Vol. 113, 01.05.2018, p. 82-96.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - High fat diet treatment impairs hippocampal long-term potentiation without alterations of the core neuropathological features of Alzheimer disease
AU - Salas, Isabel H.
AU - Weerasekera, Akila
AU - Ahmed, Tariq
AU - Callaerts-Vegh, Zsuzsanna
AU - Himmelreich, Uwe
AU - D'Hooge, Rudi
AU - Balschun, Detlef
AU - Saido, Takaomi C.
AU - De Strooper, Bart
AU - Dotti, Carlos G.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - 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.
AB - 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.
KW - Alzheimer disease
KW - Behavior
KW - Electrophysiology
KW - Magnetic resonance spectroscopy
KW - Metabolic stress
KW - Type 2 diabetes
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U2 - 10.1016/j.nbd.2018.02.001
DO - 10.1016/j.nbd.2018.02.001
M3 - Article
AN - SCOPUS:85042189782
VL - 113
SP - 82
EP - 96
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
ER -