Behavioural and transcriptomic characterization of the comorbidity between Alzheimer’s disease and Major Depression

Abstract

Major Depression (MD) is the most prevalent psychiatric disease in the population and is considered a prodromal stage of the Alzheimer s disease (AD). Despite both diseases having a robust genetic component, the common transcriptomic signature remains unknown. In this regard, we investigated the cognitive and emotional responses in 3- and 6-month-old in APP/PSEN1-Tg mutant mice, before beta-amyloid plaques were detected. Then, we studied the deregulation of genes and pathways in prefrontal cortex, striatum, hippocampus and amygdala, using transcriptomic and functional data analysis. The results demonstrated that depressive-like and anxiety-like behaviours, as well as memory impairments are already present at 3-month-old together with the deregulation of several genes and gene sets, including components of the circadian rhythms, electronic transport chain and neurotransmission. Finally, DisGeNET GSEA provides translational support for common depregulated gene sets related to MD and AD. Altogether, the results demonstrate that MD could be an early manifestation of AD.

Unraveling the Genetic Comorbidity Landscape of Alzheimer’s Disease

“…Although several longitudinal studies have identified chronic diseases as at-risk conditions for increased AD incidence, most research on the association between AD and comorbidities has focused on the impact of a single or a small number of chronic diseases. This approach overlooks other frequent co-occurrences, thus restricting researchers from deeper exploration (4,8,9). Meanwhile, the majority of studies conducted thus far have primarily focused on exploring the phenotypic relationships between AD and its associated comorbidities.…”