Maternal High-Fat Diet Worsens Memory Deficits in the Triple-Transgenic (3xTgAD) Mouse Model of Alzheimer’s Disease

Alzheimer’s disease (AD) is not normally diagnosed until later in life, although evidence suggests that the disease starts at a much earlier age. Risk factors for AD, such as diabetes, hypertension and obesity, are known to have their affects during mid-life, though events very early in life, including maternal over-nutrition, can predispose offspring to develop these conditions. This study tested whether over-nutrition during pregnancy and lactation affected the development of AD in offspring, using a transgenic AD mouse model. Female triple-transgenic AD dam mice (3xTgAD) were exposed to a high-fat (60% energy from fat) or control diet during pregnancy and lactation. After weaning (at 3 weeks of age), female offspring were placed on a control diet and monitored up until 12 months of age during which time behavioural tests were performed. A transient increase in body weight was observed in 4-week-old offspring 3xTgAD mice from dams fed a high-fat diet. However, by 5 weeks of age the body weight of 3xTgAD mice from the maternal high-fat fed group was no different when compared to control-fed mice. A maternal high-fat diet led to a significant impairment in memory in 2- and 12-month-old 3xTgAD offspring mice when compared to offspring from control fed dams. These effects of a maternal high-fat diet on memory were accompanied by a significant increase (50%) in the number of tau positive neurones in the hippocampus. These data demonstrate that a high-fat diet during pregnancy and lactation increases memory impairments in female 3xTgAD mice and suggest that early life events during development might influence the onset and progression of AD later in life.