Positive and negative early life experiences differentially modulate long term survival and amyloid protein levels in a mouse model of Alzheimer’s disease

// Sylvie L. Lesuis 1 , Herve Maurin 2 , Peter Borghgraef 2 , Paul J. Lucassen 1 , Fred Van Leuven 2 and Harm J. Krugers 1 1 Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands 2 Experimental Genetics Group - LEGTEGG, Department of Human Genetics, KU Leuven, Leuven, Belgium Correspondence to: Sylvie L. Lesuis, email: // Keywords : early life stress, early handling, biAT, Alzheimer, glucocorticoids, Gerotarget  Received : March 28, 2016 Accepted : May 12, 2016 Published : June 01, 2016 Abstract Stress has been implicated as a risk factor for the severity and progression of sporadic Alzheimer’s disease (AD). Early life experiences determine stress responsivity in later life, and modulate age-dependent cognitive decline. Therefore, we examined whether early life experiences influence AD outcome in a bigenic mouse model which progressively develops combined tau and amyloid pathology (biAT mice). Mice were subjected to either early life stress (ELS) or to ‘positive’ early handling (EH) postnatally (from day 2 to 9). In biAT mice, ELS significantly compromised long term survival, in contrast to EH which increased life expectancy. In 4 month old mice, ELS-reared biAT mice displayed increased hippocampal Aβ levels, while these levels were reduced in EH-reared biAT mice. No effects of ELS or EH were observed on the brain levels of APP, protein tau, or PSD-95. Dendritic morphology was moderately affected after ELS and EH in the amygdala and medial prefrontal cortex, while object recognition memory and open field performance were not affected. We conclude that despite the strong transgenic background, early life experiences significantly modulate the life expectancy of biAT mice. Parallel changes in hippocampal Aβ levels were evident, without affecting cognition of young adult biAT mice.