Alzheimer's disease (AD), the leading cause of dementia, has traditionally been described as a pathology primarily affecting cognitive function with impaired neuronal and glial functioning. However, recent studies suggest that more than 75% of patients exhibit early emotional perturbations and that cerebrovascular remodeling could underlie these cognitive and emotional impairments. The aim of this study was to characterize the time of onset of anxio-depressive-like phenotype in a mouse model of AD and their potential correlation with blood-brain barrier (BBB) dysfunctions already described by our group, which mainly consisted of a decrease in the vascular volume and a down- or up-regulation of transporters of Amyloid-beta peptide (Aβ) and sterols. Several behavioral tests were done in 3-month-old 3xTg-AD mice to characterize their emotional state (light-dark box, open field, splash, and forced swimming tests) and their cognitive function (novel object recognition, spontaneous Y-maze alternation tests). At the end of the behavioral evaluations, several markers of BBB structure and function were investigated in these 3xTg-AD mice (tight junctions, astrocytes, transporters, permeability, pTau, and Aβ) using immunohistochemistry and western blot. Our investigations reveal that emotional perturbations manifest as early as 3 months in the 3xTg-AD mice—before the onset of recognition memory and spatial working memory dysfunctions. Moreover, our preliminary results suggest that upregulation and downregulation of proteins in the BBB could be linked to these behavioral impairments. Thus, emotional modifications present in AD patients are found in the well-known 3xTg-AD mice, and BBB modifications could be a key mechanism underlying them.