Carbonic anhydrase inhibitors: a novel pharmacological strategy to rescue Aβ‐induced neurovascular pathology and gliosis in vivo

Cerebrovascular dysfunction (CVD) and neuroinflammation are associated and contribute to Alzheimer's disease (AD) progression. Most AD cases also present cerebral amyloid angiopathy (CAA), characterized by amyloid beta (Aβ) deposits at the brain vasculature, which trigger CVD and dysregulated brain clearance. In addition, CVD and altered clearance worsen vascular Aβ deposition, inducing cellular stress, neuroinflammation, metabolic waste accumulation, vascular permeability, infiltration of blood‐borne cells, and eventually leading to neurodegenerative processes and cognitive impairment. Endothelial cells (ECs) and glial cells are major players in mediating vascular fitness and brain clearance, promoting the removal of toxic material from the brain, including Aβ. Our previous findings demonstrated that Aβ elicits mitochondrial dysregulation and caspase‐mediated apoptosis in ECs and glial cells. Moreover, we showed that acetazolamide (ATZ) and methazolamide (MTZ), FDA‐approved carbonic anhydrase inhibitors (CAIs), employed in non‐AD related conditions, hinder these pathological events.