Reduction of β-amyloid and γ-secretase by calorie restriction in female Tg2576 mice

Abstract

Research indicates that female risk of developing Alzheimer’s disease (AD) is greater than that of males. Moderate reduction of calorie intake, known as calorie restriction (CR), reduces pathology in AD mouse models, and is a potentially translatable prevention measure for individuals at-risk for AD, as well as an important tool for understanding how the brain endogenously attenuates age-related pathology. Whether sex influences the response to CR remains unknown. In this study, we assessed the effect of CR on beta-amyloid peptide (Aβ) pathology and hippocampal CA1 neuron specific gene expression in the Tg2576 mouse model of cerebral amyloidosis. Relative to ad libitum (AL) feeding, CR feeding significantly reduced hippocampal Aβ burden in 15 month old female, but not age-matched male, Tg2576 mice. Sustained CR also significantly reduced expression of presenilin enhancer 2 (Psenen) and presenilin 1 (Ps1), components of the γ-secretase complex, in Tg2576 females. These results indicate that long-term CR significantly reduces age-dependent female Tg2576 Aβ pathology, which is likely to involve CR-mediated reductions in γ-secretase-dependent amyloid precursor protein (APP) metabolism.

Caloric restriction preserves memory and reduces anxiety of aging mice with early enhancement of neurovascular functions

“…Animal studies further demonstrated that Aβ plaque formation is an activity dependent process associated with AG [49, 51]. Therefore, increased oxidative metabolism in cognition-related regions may decrease AG and thus reduce the risk for AD, consistent with the findings in CR mice [23, 24]. …”

“…Enhanced memory in elderly humans and aging animals has also been reported with CR [19–22]. In animal models of AD, CR reduces amyloid beta (Aβ) deposition and preserves memory [23, 24]. However, the impact of CR on CBF and BBB, and the interplay between in vivo neurovascular functions, cognitive aging, and mental health, remain unknown.…”

Maternal choline supplementation in a mouse model of Down syndrome: Effects on attention and nucleus basalis/substantia innominata neuron morphology in adult offspring

“…In addition to the different behavioral and cognitive demands, the series of attention tasks used in the present study required a more stringent and longer period of food restriction than the water maze procedure. A growing literature suggests that calorie restriction itself can be neuroprotective in mouse models of neurodegenerative disorders (Contestabile, 2009; Schafer et al, 2015a, 2015b), and thus may have interacted with the effects of MCS and/or the trisomy. BFCN morphometry may also have been influenced by social isolation.…”

Metabolic study of Alzheimer’s disease using mutant C. elegans

“…Meanwhile, improvements in AD symptoms after caloric restriction, or a reduction in glucose dependent energy metabolism supports the hypothesis that a decrease in glucose metabolism is protective [31,32,605,606]. Overall, these observations identify glucose energy metabolism as an important target of study to improve our understanding of AD progression.…”