Caloric restriction attenuates amyloid deposition in middle-aged dtg APP/PS1 mice

Abstract

Caloric restriction (CR) mitigates neurological damage arising from aging and a variety of other sources, including neuropathology in young adult mice that express single and double transgenic (tg) mutations associated with Alzheimer disease (AD). To evaluate the potential of CR to protect against relatively heavy AD-type pathology, middle-aged (13-14-month-old) mice that co-express two mutations related to familial AD, amyloid precursor protein (APP) and presenilin 1 (PS1), were fed balanced diets with 40% fewer calories than ad libitum-fed controls. Following 18 weeks of treatment, mice were killed and brains were processed for quantification of total volume of amyloid-beta (Abeta) in the hippocampal formation and the overlying neocortex. Computerized stereology confirmed that CR reduced the total Abeta volume by about one-third compared to that in age-matched controls. Thus, CR appears to attenuate the accumulation of AD-type neuropathology in two cortical brain regions of middle-aged dtg APP/PS1 mice. These findings support the view that CR could be a potentially effective, non-pharmacology strategy for reducing relatively heavy Abeta deposition in older adult dtg APP/PS1 mice, and possibly afford similar protection against the onset and progression of AD in older adult humans.

Figure 1

Mean (SEM) body weight on male C57BL/6J mice begun on calorie restriction (CR) at 13-14 mo of age. Body weight was significantly reduced in CR mice beginning 4 weeks after initiation of 40% CR phased in with 10% restriction each week (two-tailed t-test comparisons at each week, ps <0.05). Mean (SEM) body weight on male C57BL/6J mice following CR starting at 13-14 mo of age.

Figure 2

Congo red stained amyloid deposit with overlaid point-grid (area per point = 50 um²) for quantification of amyloid load (100× oil, n.a. 1.4).