Drug repositioning in Alzheimer’s disease: a vascular perspective targeting the NO-cGMP pathway

Alzheimer’s disease (AD) continues to represent a major unmet medical need despite advances in the understanding of its pathophysiology. For more than two decades, available therapeutic options have been limited to symptomatic treatments, including acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and the N-methyl-D-aspartate (NMDA) receptor antagonist memantine. More recently the approval of monoclonal antibodies, such as lecanemab and donanemab, has marked a shift in the therapeutic approach by targeting underlying disease mechanisms. However, their clinical impact is still limited, highlighting the need to explore new therapeutic strategies.1