| First Author | Mazzei G | Year | 2021 |
| Journal | Aging Cell | Volume | 20 |
| Issue | 8 | Pages | e13429 |
| PubMed ID | 34245097 | Mgi Jnum | J:311367 |
| Mgi Id | MGI:6755063 | Doi | 10.1111/acel.13429 |
| Citation | Mazzei G, et al. (2021) A high-fat diet exacerbates the Alzheimer's disease pathology in the hippocampus of the App(NL-F/NL-F) knock-in mouse model. Aging Cell 20(8):e13429 |
| abstractText | Insulin resistance and diabetes mellitus are major risk factors for Alzheimer's disease (AD), and studies with transgenic mouse models of AD have provided supportive evidence with some controversies. To overcome potential artifacts derived from transgenes, we used a knock-in mouse model, App(NL-F/NL-F) , which accumulates Abeta plaques from 6 months of age and shows mild cognitive impairment at 18 months of age, without the overproduction of APP. In the present study, 6-month-old male App(NL-F/NL-F) and wild-type mice were fed a regular or high-fat diet (HFD) for 12 months. HFD treatment caused obesity and impaired glucose tolerance (i.e., T2DM conditions) in both wild-type and App(NL-F/NL-F) mice, but only the latter animals exhibited an impaired cognitive function accompanied by marked increases in both Abeta deposition and microgliosis as well as insulin resistance in the hippocampus. Furthermore, HFD-fed App(NL-F/NL-F) mice exhibited a significant decrease in volume of the granule cell layer in the dentate gyrus and an increased accumulation of 8-oxoguanine, an oxidized guanine base, in the nuclei of granule cells. Gene expression profiling by microarrays revealed that the populations of the cell types in hippocampus were not significantly different between the two mouse lines, regardless of the diet. In addition, HFD treatment decreased the expression of the Abeta binding protein transthyretin (TTR) in App(NL-F/NL-F) mice, suggesting that the depletion of TTR underlies the increased Abeta deposition in the hippocampus of HFD-fed App(NL-F/NL-F) mice. |
