What are immune treatments for Alzheimer's (Alzheimer's disease)?

From the Guidelines

Immune treatments for Alzheimer's disease, such as aducanumab, lecanemab, and donanemab, are the most effective options for reducing inflammation and modifying the immune response in the brain, and should be considered as first-line treatments for early symptomatic Alzheimer's disease, including mild cognitive impairment (MCI) or mild dementia caused by AD, as recommended by the Global CEO Initiative on Alzheimer's Disease 1. These medications are typically administered via intravenous infusion every 2-4 weeks, with aducanumab given at a dose of 10 mg/kg monthly, and lecanemab administered at 10 mg/kg every two weeks. The treatments work by binding to amyloid beta aggregates and facilitating their removal by activating microglial cells, the brain's immune cells. Other immune-based approaches include anti-inflammatory medications, microglial modulators, and vaccines designed to stimulate the immune system to clear toxic proteins. Patients receiving these treatments should be monitored for side effects, particularly ARIA (amyloid-related imaging abnormalities), which can cause brain swelling or small hemorrhages. Biomarker confirmation of amyloid pathology is required before initiation of these treatments, and blood-based biomarkers, such as the Aβ42/40 ratio, phosphorylated tau (p-tau), and neurofilament light-chain (NfL), can be used to determine the presence of amyloid pathology 1. The use of these biomarkers can help identify patients who are most likely to benefit from immune treatments, and can also help monitor the effectiveness of these treatments. Early diagnosis is crucial for optimal treatment outcomes, and the immune system plays a significant role in Alzheimer's pathology, as chronic neuroinflammation contributes to disease progression, making immune modulation a promising therapeutic strategy 1. Some key points to consider when using immune treatments for Alzheimer's disease include:

• The importance of early diagnosis and treatment, as these treatments are most effective in the early stages of the disease
• The need for biomarker confirmation of amyloid pathology before initiation of treatment
• The potential for side effects, such as ARIA, and the need for regular monitoring
• The importance of considering the individual patient's needs and circumstances when selecting a treatment option.

From the Research

Immune Treatments for Alzheimer's Disease

• Current treatment for Alzheimer's disease is only symptomatic and has modest benefits, leading to a focus on developing disease-modifying therapies 2
• Therapies targeting amyloid β have been the primary focus, but recent failures in phase III trials have shifted attention to tau-targeting therapies 2
• Immunotherapies, including monoclonal antibodies and vaccines, are being explored as potential treatments for Alzheimer's disease 2, 3

Monoclonal Antibodies

• Several monoclonal antibodies, such as aducanumab, lecanemab, and donanemab, have been approved for the treatment of Alzheimer's disease 3, 4
• These antibodies target amyloid β and have shown promise in reducing cognitive decline and amyloid plaque burden 3, 4
• However, they also carry a risk of amyloid-related imaging abnormalities and infusion reactions 4, 5

Anti-Tau Therapies

• Anti-tau therapies, including monoclonal antibodies and vaccines, are in the early stages of clinical research 2
• Four monoclonal antibodies (Gosuranemab, Tilavonemab, Semorinemab, and Zagotenemab) and one anti-tau vaccine (AADvac1) have reached phase II trials 2
• These therapies aim to target tau protein, which is thought to be more closely correlated with cognitive decline than amyloid β 2

Future Directions

• Further research is needed to fully understand the potential of immune treatments for Alzheimer's disease 2, 3, 6
• The development of subcutaneous formulations and blood-based biomarkers may increase accessibility and reduce the demands on healthcare systems associated with these agents 4
• Combination therapies targeting multiple pathogenic factors, such as amyloid β, tau, and neuroinflammation, may hold promise for future treatment strategies 6