<p>Monoclonal antibody (mAb) therapies represent a new frontier in Alzheimer’s disease (AD) treatment, offering targeted approaches to reduce amyloid-β (Aβ) burden in the brain as an avenue toward slowing cognitive and functional decline. This article explores the potential benefits and limitations of these disease-modifying treatments in clinical practice.</p>

Anti-amyloid mAb agents target aspects of Aβ pathology in the brain, with the latter understood to be a part of the AD pathophysiologic cascade. In large phase 3 clinical trials of mAb treatments that have since been US Food and Drug Administration (FDA) approved for clinical use (ie, lecanemab and donanemab), in patients with mild cognitive impairment or mild dementia due to AD, treatment resulted in an approximately 30% slowing of cognitive decline over 18 months compared with patients who received placebo.

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However, there are some risks associated with using these medications. There can be infusion reactions in approximately 25% of cases, and these reactions are most common early in the treatment course and are generally self-limited and manageable. The main potential side effects of mAb therapies that require additional attention are amyloid-related imaging abnormalities (ARIA). mAb treatments work by helping to clear Aβ plaques from the brain. This process can also impact the blood vessels and predispose them to being “leaky,” potentially resulting in microhemorrhages and/or superficial siderosis (referred to as ARIA-H) or edema and/or effusions (referred to as ARIA-E).

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We know of some risk factors that can increase the likelihood of developing ARIA, such as the presence of the APOE ɛ4 allele. We also know that baseline magnetic resonance imaging findings of microhemorrhages or siderosis in the brain prior to initiating treatment represent additional risk factors for developing ARIA. Further, there is emerging research that points to hypertension as another risk factor, in this case one that could be modified.

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Another important thing for patients to consider as they are navigating their options is that, while these anti-amyloid therapies represent a step forward, they may not be the best approach for every patient with AD. Patients have to be in the early symptomatic stages of AD, meaning that they have been diagnosed with mild cognitive impairment or mild dementia due to AD. There are no current data to support the efficacy of these therapies in patients who have moderate or severe dementia due to AD. Patients also need a biomarker demonstration of an abnormal burden of amyloid plaques in the brain for appropriate targeting of mAb therapy. Most commonly, this biomarker support is being determined through positron emission tomography or cerebrospinal fluid testing. There is active discussion about the potential use of high-quality blood biomarkers as an alternative to serve this purpose, acknowledging that further research is ongoing, which may impact modes of practice in the future. It is also important to have a thorough medical history and a high-quality baseline magnetic resonance imaging scan to evaluate for findings that could impact eligibility.

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Finally, treatment with mAbs benefits from shared decision making, as using these therapies involves a significant commitment for patients. However, if patients meet the criteria for eligibility, understand the risks and benefits of using these therapies, and have the care partner and logistical support to proceed, mAb treatments can be a good option for some individuals in the early stages of AD.