Alzheimer's disease (AD) is the most prevalent form of dementia, affecting over 47 million people globally and projected to exceed 130 million by 2050. The economic burden of AD management is estimated at $355 billion. This review evaluates the pathophysiology of AD, focusing on the therapeutic efficacy and limitations of existing drugs, including acetylcholinesterase inhibitors (AChEIs) and N-methyl-D-aspartate receptor (NMDAR) modulators. The hypothesis that amyloid-β (Aβ) and tau are key targets for therapeutic intervention is critically analyzed, particularly in the context of anti-Aβ monoclonal antibodies (MABs) such as aducanumab, lecanemab, and donanemab. The review challenges the notion that targeting Aβ will benefit most AD patients and highlights the need for alternative drug targets and the importance of treating comorbidities like hypertension, diabetes, obesity, and depression. The article also discusses the limitations of current diagnostic tools and the potential of new biomarkers for earlier diagnosis and treatment assessment. Despite the current lack of disease-modifying treatments, ongoing research aims to identify new therapeutic targets and improve patient outcomes.Alzheimer's disease (AD) is the most prevalent form of dementia, affecting over 47 million people globally and projected to exceed 130 million by 2050. The economic burden of AD management is estimated at $355 billion. This review evaluates the pathophysiology of AD, focusing on the therapeutic efficacy and limitations of existing drugs, including acetylcholinesterase inhibitors (AChEIs) and N-methyl-D-aspartate receptor (NMDAR) modulators. The hypothesis that amyloid-β (Aβ) and tau are key targets for therapeutic intervention is critically analyzed, particularly in the context of anti-Aβ monoclonal antibodies (MABs) such as aducanumab, lecanemab, and donanemab. The review challenges the notion that targeting Aβ will benefit most AD patients and highlights the need for alternative drug targets and the importance of treating comorbidities like hypertension, diabetes, obesity, and depression. The article also discusses the limitations of current diagnostic tools and the potential of new biomarkers for earlier diagnosis and treatment assessment. Despite the current lack of disease-modifying treatments, ongoing research aims to identify new therapeutic targets and improve patient outcomes.