ADIPOSE-BRAIN AXIS IN AGEING AND ALZHEIMER-S DISEASE: GENOTYPE- AND AGE-DEPENDENT VISCERAL ADIPOSE HYPERTROPHY AND BEHAVIOURAL CORRELATIONS IN MALE 3XTG-AD MICE VERSUS NORMAL AGEING

Alzheimer’s disease (AD) is associated with systemic metabolic alterations, yet how white adipose tissue (WAT) remodelling relates to behavioural phenotype across normal and pathological ageing remains unclear. We aimed to determine whether triple-transgenic 3xTg-AD mice show genotype- and age-dependent visceral WAT phenotype associated with their overweight and as compared with non-transgenic wild-type (WT) counterparts undergoing normal ageing. In addition, we analysed adipose–behaviour correlations within and across genotypes. Male WT and 3xTg-AD mice were assessed at two ages/stages of disease using the corner test and open field in a two/days paradigm to quantify exploratory activity and novelty-related anxiety-like behaviours. Visceral WAT depots were dissected and weighed for absolute weight and depot index. Behavioural results confirmed genotype- and age-related differences in exploration and habituation since the onset of disease, which worsen at advanced stages. Classical haematoxylin and eosin histopathological analysis, followed by Fiji/ImageJ quantification, unveiled distinct adipocyte morphology and size distributions. The age/related hypertrophic adipose phenotype found in WT animals with normal ageing, with larger adipocytes emerging in visceral depots, was exhibited in young male 3xTg-AD mice and worsened with the disease. Correlation analysis of adipose and behavioural variables was expressed in WT males and when considered for the pooled cohort. The correlations within the 3xTg-AD genotype were less consistently expressed, probably due to their early hypertrophic phenotype. These findings indicate that AD genotype modifies age-related adipose remodelling and may alter systemic correlates of behaviour, supporting investigation of the adipose–brain axis in aging and AD/disease.