Cerebrovascular damage and dysfunction have been suggested to be closely related to pathophysiology of Alzheimer's disease (AD). The effect of adiponectin (APN), an adipocyte-secreted hormone, on the risk and progression of AD patients remains unclear. APN has been demonstrated to play a protective role in peripheral vasculature, while little is known about its impact on cerebrovascular dysfunction in AD. In this study, we examined the cerebrovascular integrity of wildtype, 5xFAD, APN knockout (APN-/-), and APN-deficient 5xFAD (5xFAD;APN-/-) mice in terms of blood-brain barrier (BBB) permeability, cerebral vascular angiopathy (CAA), and tight junction proteins (TJPs) on endothelial cells. Fluorescein sodium salt penetration assay revealed that 5xFAD;APN-/- mice exhibited higher BBB permeability than 5xFAD mice at 3, 6, and 9 months of age. Endogenous IgG immunofluorescence staining further confirmed greater IgG extravasation from the circulation to brain parenchyma in 5xFAD;APN-/- mice compared to 5xFAD mice. Increased amount of Aβ was deposited in cerebral vessels of 5xFAD;APN-/- mice compared to that of 5xFAD mice at 6 months of age, indicating aggravated CAA pathology. Immunofluorescence staining of TJPs, claudin-5 and occludin, revealed less expression levels in both 5xFAD and APN-/- mice than wildtype mice. Notably, 5xFAD;APN-/- mice displayed the most significant reduction in TJPs. In conclusion, our findings indicate that APN deficiency exacerbates BBB leakage, CAA pathology, and TJPs loss in AD mice. This study suggests that APN deficiency worsens cerebrovascular dysfunction in AD, underscoring the potential of enhancing APN signaling activity as a therapeutic strategy for AD.