Key result
Adiponectin deficiency increases blood-brain barrier leakage ~50% in Alzheimer mice, whereas supplementation restores cerebral flow.
Cerebrovascular dysfunction is worsened in Alzheimer’s by adiponectin deficiency, highlighting potential therapies.
Cerebrovascular dysfunction (CVD) is increasingly recognized as a contributor to Alzheimer's disease (AD) progression. Adiponectin (APN), an adipocyte-derived hormone with vasoprotective properties in the periphery, has an unclear impact on AD-related cerebrovascular integrity. We showed that APN-deficient mice exhibited reduced resting cerebral blood flow (CBF), impaired neurovascular coupling (NVC), disrupted blood-brain barrier (BBB), and enhanced cerebral amyloid angiopathy (CAA), which are CVD characteristics that also observed in 5xFAD mice, a model of AD. Notably, APN-deficient 5xFAD mice displayed more severe CVD than 5xFAD mice alone. Transcriptomic analysis of brain endothelial cells (ECs) identified dysregulated biological processes and key signaling pathways underlying EC dysfunction. Importantly, the administration of APN restored CBF and NVC in 5xFAD mice, and prevented tight junction protein (TJP) loss and barrier breakdown in Aβ40-exposed primary ECs. These results highlight the potential of alleviating CVD through targeting ECs with APN as a promising therapeutic strategy to delay the onset and mitigate the progression of AD.
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Zou et al. (2026) studied Alzheimer's disease and cerebrovascular dysfunction (preclinical mouse model). Adiponectin (APN) deficiency / Adiponectin administration vs. Wildtype and 5xFAD mice / vehicle control was evaluated on Cerebrovascular dysfunction (resting cerebral blood flow, neurovascular coupling, and blood-brain barrier permeability via NaFl extravasation) (Approximately 1.5-fold increase in NaFl extravasation at 3 months in 5xFAD;APN-/- mice, p=<0.05). Adiponectin deficiency accelerated blood-brain barrier leakage (~1.5-fold NaFl extravasation at 3 months) and neurovascular impairment in 5xFAD mice, while adiponectin administration restored cerebral blood flow.
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