P4‐166: Beneficial Effects of a Permament Family Structure: Behavioural and Neuropathological Studies in Triple Transgenic 3xtgad Mice for Alzheimer's Disease

Environmental enrichment has emerged as a potential non-invasive strategy that might influence the onset and progression of neurodegenerative pathologies including Alzheimer's disease. Among social factors, many studies have reported the association between mild-life marital status and cognitive function in later life. Thus, living as a couple and the quality of the relationship are both positively correlated with health and longevity. In contrast, an increased risk of dementia from living without a partner, either as single, divorced, or unmarried has been also demonstrated. The aim of the present work was to study the effects of a permanent family structure on the progress of both the behavioural and neuropathological hallmarks of triple transgenic 3xTg-AD mice, an animal model for Alzheimer's disease. For that purpose, we performed a longitudinal follow-up study of permanent family units (couple of breeders and offspring) living together from adulthood until their elderly (18 month-old) as compared to standard social housing conditions (units of 4-6 animals of the same gender). Non-transgenic mice were studied in parallel. The effects of the social condition on the cognitive deficits, BPSD-like symptoms and neuropathological hallmarks were studied at different stages of the disease. The family structure was able to modify the emotional phenotype (neophobia and other anxiety-like symptoms) and to improve the gender-dependent survival-curves of 3xTg-AD mice. Brain coronal-sections were obtained and stained by immunohistochemistry for iba-1 to identify microglia/macrophage reactivity, ß-amyloid (Aß) protein-deposition and tau for identification of neurofibrillary tangle formation. Our observations showed that 12 month-old 3xTg-AD mice in a family structure showed a significant decrease in microglial reactivity that correlated with a decrease in Aß-deposition and tau expression as compared with 3xTg-AD mice living in standard social housing conditions. These beneficial effects were diminished with the progress of the disease, since the differences between animals at the most advanced stages (18 month-old) were minimal. Our data provide evidence that environmental enrichment by means of a permanent family structure is able to counteract behavioural and neuropathological hallmarks of the disease with higher success in the moderate stages of the disease. Financial support: Fundació La Marató TV3-062930.