Isolation housing exacerbates Alzheimer’s Disease phenotype in aged APP KI mice

Abstract

AbstractIn January 2018, Britain was the first in the world to adopt a Minister of Loneliness. This illustrates the changing view on loneliness: being lonely is not just a feeling of a lack of companionship, but also a serious health problem. For example, we know that loneliness is as bad as smoking 15 cigarettes a day. Moreover, research has shown that lonely people express higher levels of cortical amyloid. Amyloid burden is an important marker of Alzheimer’s Disease (AD), a chronic neurodegenerative disease and the main cause of dementia worldwide. Together with other findings a link between loneliness, (perceived) social isolation and AD is now undeniable, but it is hard to tell from human studies whether it is the cause or the effect of AD. We need standardized animal studies to answer this question.In an effort to study how social isolation and AD interact, we used APP KI mice bearing human transgenes known to cause AD, and isolated part of the mice in order to mimic loneliness in late-life while part of them remained group-housed. We next looked at the effects of isolation on the behaviour and symptomatology typically present in AD patients to tap cognition.Our study reveals mixed results. Results indicate that at before isolation, at the age of 16 and 24 months, APPNL/NLand APPNL-G-F/NL-G-Fmice do not differ to a significant extent on both the behavioural level. The APPNL-G-F/NL-G-Fdifferentiated slightly worse between the conditioned context and a new context compared to the APPNL/NLmice. However, the difference appeared to be more pronounced after a period of social isolation. Social isolation had distinct effects on the AD-related anxiogenic and dementia-like phenotype. Spatial learning in the MWM task revealed distinct differences between our two models. After isolation APPNL-G-F/NL-G-Fmice used less spatial search strategies, compared to control mice, thus reflecting perseveration and less behavioural flexibility due to the isolation period.