High-fat diet-induced memory impairment in triple-transgenic Alzheimer's disease (3xTgAD) mice is independent of changes in amyloid and tau pathology

Abstract

Obesity and consumption of a high-fat diet are known to increase the risk of Alzheimer's disease (AD). Diets high in fat also increase disease neuropathology and/or cognitive deficits in AD mouse models. However, the effect of a high-fat diet on both the neuropathology and memory impairments in the triple-transgenic mouse model of AD (3xTgAD) is unknown. Therefore, groups of 2-month-old male 3xTgAD and control (non-Tg) mice were maintained on a high-fat or control diet and memory was assessed at the age of 3–4, 7–8, 11–12, and 15–16 months using a series of behavioral tests. A comparable increase in body weight was observed in non-Tg and 3xTgAD mice after high-fat feeding at all ages tested but a significantly greater increase in epididymal adipose tissue was observed in 3xTgAD mice at the age of 7–8, 11–12, and 15–16 months. A high-fat diet caused memory impairments in non-Tg control mice as early as the age of 3–4 months. In 3xTgAD mice, high-fat consumption led to a reduction in the age of onset and an increase in the extent of memory impairments. Some of these effects of high-fat diet on cognition in non-Tg and 3xTgAD mice were transient, and the age at which cognitive impairment was detected depended on the behavioral test. The effect of high-fat diet on memory in the 3xTgAD mice was independent of changes in AD neuropathology as no significant differences in (plaques, oligomers) or tau neuropathology were observed. An acute increase in microglial activation was seen in high-fat fed 3xTgAD mice at the age of 3–4 months but in non-Tg control mice microglial activation was not observed until the age of 15–16 months. These data indicate therefore that a high-fat diet has rapid and long-lasting negative effects on memory in both control and AD mice that are associated with neuroinflammation, but independent of changes in beta amyloid and tau neuropathology in the AD mice.

Effects of diet-induced obesity and voluntary exercise in a tauopathy mouse model: Implications of persistent hyperleptinemia and enhanced astrocytic leptin receptor expression

“…Although the evaluation of HCD effects on cognitive and behavioral functions must be important as same as pathological changes, we did not analyze those, because old PS19 mice showed motor symptoms (paralysis). Recently, Knight et al (2014) reported that high-fat diet induced memory impairment without enhanced amyloid or tau pathology in 3xTgAD mice (APP S we, PS1 M146 , TAU P301L ). This indicates that obesity itself might affect the cognitive functions without enhanced AD pathological changes.…”

Alzheimer’s disease and gut microbiota

“…Epidemiological survey shows that consumption of too much saturated fat is a high risk factor of AD (Eskelinen et al, 2008;Laitinen et al, 2006). High fat diet could induce CNS A accumulation and memory impairment in mice (Knight et al, 2014;Refolo et al, 2001). More and more evidences suggest that low calorie diet can delay the progress of brain aging (Martin et al, 2006).…”

Hypothalamic-pituitary-adrenal axis hypersensitivity in female rats on a post-weaning high-fat diet after chronic mild stress

“…HFD was shown to have rapid and long-lasting negative effects on memory in model mice with and without Alzheimer's disease (34). The open field test is a classic experimental method for behavioral evaluation, including locomotor activity and exploratory behavior, and the electric maze test is used to assess learning and memory.…”