| First Author | Walker JM | Year | 2017 |
| Journal | Neurobiol Dis | Volume | 100 |
| Pages | 87-98 | PubMed ID | 28108292 |
| Mgi Jnum | J:260942 | Mgi Id | MGI:6141426 |
| Doi | 10.1016/j.nbd.2017.01.004 | Citation | Walker JM, et al. (2017) Reversal of high fat diet-induced obesity improves glucose tolerance, inflammatory response, beta-amyloid accumulation and cognitive decline in the APP/PSEN1 mouse model of Alzheimer's disease. Neurobiol Dis 100:87-98 |
| abstractText | This study assessed the extent to which high fat diet (HFD)-induced beta-amyloid accumulation and cognitive decline in APP/PSEN1 mice are reversible through control of fat intake. Ten months of HFD (60% calories from fat) led to significant deficits in a 2-trial Y maze task, and nest building assay, and decreased voluntary locomotor activity. The HFD induced an inflammatory response, indicated by increased expression of several inflammatory markers. Substituting a low fat diet led to pronounced weight loss and correction of glucose intolerance, decreases in the inflammatory response, and improved performance on behavioral tasks in both wild-type and APP/PSEN1 transgenic mice. Insoluble beta-amyloid levels, and extent of tau phosphorylation were also lower following dietary reversal in APP/PSEN1 mice compared to high fat-fed animals, indicating that the inflammatory response may have contributed to key pathogenic pathways in the Alzheimer''s disease model. The data suggest that weight loss can be a vital strategy for cognitive protection, but also highlight potential mechanisms for intervention when sustained weight loss is not possible. |
