Given the multifactorial and complex nature of AD, polypharmacology has emerged as a viable therapeutic strategy with clinical applications. Namzaric®, a combination of donepezil and memantine, was approved by the FDA in 2014 ; however, its marketing authorization was denied by the European Medicines Agency (EMA). Combination therapies, especially those involving antibodies, present significant challenges due to their complexity, high costs, and specialized healthcare professionals' requirement for intravenous administration . In contrast, the polypharmacological approach based on multi-target-directed ligands (MTDLs)-single small molecules capable of modulating multiple targets within the AD pathological network-offers a more promising strategy . MTDLs demonstrate advantages in terms of efficacy, reduced toxicity, and lower overall costs .