Can A Synergistic Therapy Be Administered Against Both Aβ and Tau Aggregates in Alzheimer’s Disease?

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and behavioral changes, and is pathologically defined by the accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles in the brain. The amyloid cascade and tau hypotheses describe complementary mechanisms contributing to disease progression, yet current therapies have historically focused on targeting Aβ alone, with limited clinical success. These outcomes highlight the need for more comprehensive treatment approaches that address multiple pathogenic pathways. This review examines current evidence on Aβ and tau pathology, evaluates therapeutic strategies targeting each pathway, and assesses the scientific feasibility, challenges, and limitations of synergistic dual-target approaches in Alzheimer’s disease. Genetic risk factors, including apolipoprotein E APOE4 polymorphism, transgenic mouse models, approved and experimental immunotherapies, and emerging biomarkers such as phosphorylated tau-217 (p-tau217) are discussed. While recent antiamyloid monoclonal antibodies have shown modest clinical benefit, the interaction between Aβ and tau pathology suggests that combination therapy may offer improved disease progression. However, there are still several mechanistic, pathological, and safety challenges. Further research is required to determine whether dual-target therapies can be translated into effective and safe treatment for Alzheimer’s disease.