The Potential Use of Matrix Metalloproteinases in Alzheimer's Disease Therapy

Alzheimer's disease is the most common cause of dementia and one of the greatest challenges of current medicine. Its pathophysiology is complex, involving β-amyloid deposition, tau hyperphosphorylation, chronic neuroinflammation, and progressive neuronal loss. Despite the introduction of novel therapies, treatment efficacy remains limited, prompting the search for alternative therapeutic targets. One promising area of research focuses on matrix metalloproteinases-proteolytic enzymes involved in tissue remodeling, synaptic plasticity, and inflammatory responses. In the context of AD, MMPs may exert both protective effects, through amyloid degradation, and detrimental effects such as blood-brain barrier disruption and amplification of neuroinflammatory damage. Understanding the dual and context-dependent roles of MMPs may help explain past translational failures and enable the development of more selective, stage-dependent therapeutic strategies. This article is a narrative review summarizing current evidence on the roles of MMPs in AD, with a particular focus on their therapeutic modulation and potential implications for future clinical research. Insights into MMP biology may ultimately guide the design of interventions with improved efficacy and safety for patients with AD.