Alzheimer’s disease, the most prevalent form of age-related dementia, is like a maze with two main obstacles: amyloid-β plaque deposits and hyperphosphorylated tau protein, resembling roadblocks. While previous treatments only provided partial relief, new disease-modifying therapies (DMTs) are taking a different approach. Anti-amyloid-β monoclonal antibodies (mabs) like aducanumab and lecanemab are at the forefront of this revolutionary treatment. By targeting the clearance of Aβ, these mabs aim to change the underlying pathology of AD, removing those roadblocks. Recent studies have shown promising results in clinical trials, indicating that immunotherapy may hold the key to battle Alzheimer’s disease. This review delves into the impact of aducanumab and lecanemab on AD pathology and clinical profiles, providing valuable evidence for their application. Additionally, it explores the lessons learned from these trials, shedding light on therapeutic and adverse effects. Dive into the fascinating realm of AD research and uncover the potential of these anti-Aβ mabs!

Alzheimer’s disease (AD) is the most prevalent form of age-related dementia in the world, and its main pathological features consist of amyloid-β (Aβ) plaque deposits and neurofibrillary tangles formed by hyperphosphorylated tau protein. So far, only a few AD treatments approved have been applied in the clinic, but the effects of these drugs are limited only for partial symptomatic relief to patients with AD and are unable to alter AD progression. Later, all efforts for AD treatments with targeting the pathogenic factors were unsuccessful over the past decades, which suggested that the pathogenesis of AD is complex. Recently, disease-modifying therapies (DMTs) that can change the underlying pathophysiology of AD, with anti-Aβ monoclonal antibodies (mabs) (e.g., aducanumab, bapineuzumab, gantenerumab, solanezumab, and lecanemab) have been developed successively and conducted in clinical trials based on the theory that a systemic failure of cell-mediated Aβ clearance contributes to AD occurrence and progression. In the review, we summarized recent studies on the therapeutic effects and clinical trial results of these mabs in patients with AD. Specifically, we focused on the discussion of the impact of aducanumab and lecanemab on AD pathology and clinical profiles. The review provides a possible evidence for applying immunotherapy with anti-Aβ mabs in AD and analyzes lessons learned from these clinical trials in order to further study the therapeutic and adverse effects of these anti-Aβ mabs on AD.

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