A high-fat diet exacerbates the Alzheimer's disease pathology in the hippocampus of the App[NL-F/NL-F] knock-in mouse model

To investigate the effects of diabetic conditions on the development of AD pathology, we fed wild-type and Alzheimer's disease model (App[NL-F/NL-F]) mice with control or high fat diet from 6 months after birth for 12 months, then examined behavior, brain pathology and gene expression profiles. Both groups of mice fed with high fat diet exhibited diabetic conditions, and App[NL-F/NL-F] mice exhibited aggravated cognitive impairment with enhanced Alzheimer's disease pathology. Six month-old male wild-type and App[NL-F/NL-F] mice harboring two pathogenic App-knock-in mutations, that promote aggressive amyloidosis by increasing total Aβ production (Swedish mutation KM670/671NL) and increasing the Aβ42/Aβ40 ratio (Iberian mutation I716F) under the control of the endogenous APP promoter, were divided into two groups (3 mice for each group), and control groups of mice were fed with control diet and HFD groups of mice were fed with high fat diet for 12 months.