Chinese Medical Journal Review highlights the role of adaptive immunity in Alzheimer’s disease

Alzheimer’s disease (AD) is a devastating condition that affects more than 55 million people globally and accounts for the majority of dementia cases. With aging populations, its impact on families, health systems, and societies continues to grow. Despite decades of research, there is still no cure, and available treatments offer only modest benefits. Understanding its root causes remains one of the greatest challenges in medicine.

Scientists have long known that AD is linked to the buildup of harmful proteins in the brain and the gradual loss of nerve cells. One of these proteins, amyloid, clumps together outside brain cells to form sticky plaques, while another protein, tau, twists into tangles inside the cells. Together, these changes disrupt communication between neurons and contribute to memory loss. In recent years, ongoing brain inflammation has also been recognized as a key feature. Until now, this inflammation was thought to be mainly caused by the brain’s first line of defense, but new evidence suggests that other parts of the immune system can also play a significant role. This insight could transform our understanding of AD and inspire new treatment approaches.

To facilitate further understanding, researchers from the Department of Neurology, Fujian Medical University Union Hospital, and the Fujian Key Laboratory of Molecular Neurology in China reviewed decades of studies examining the role of adaptive immunity in AD. Their review, led by Dr. Xiaochun Chen, was published in the Chinese Medical Journal and made available online on August 5, 2025. “AD has long been viewed mainly through the lens of amyloid, tau, and innate immunity,” says Dr. Chen. “Our review shows that adaptive immune cells, such as T and B cells, are also deeply involved, and this opens up new ways of thinking about how the disease develops and how it might be treated.”

The adaptive immune system is best known for mounting long-term, targeted responses through specialized cells called T and B cells. In Alzheimer’s, these cells appear to cross into the brain through a weakened blood–brain barrier. Once inside, they interact with brain cells in complex ways. Some T cells release inflammatory molecules that worsen damage, while others seem to have protective effects. Likewise, B cells may contribute to harmful immune reactions but can also help clear toxic proteins. “Adaptive immunity appears to act like a double-edged sword,” says Dr. Chen. “Some immune cells seem to speed up memory loss and brain damage, while others may help protect against it. Learning how to tip the balance toward the helpful side is an urgent goal for future research.”

These insights have important implications for therapy. Immunotherapies that target amyloid have shown mixed results, with drugs such as aducanumab and lecanemab sparking both hope and controversy. The review suggests that a broader approach—one that also considers adaptive immune responses—could provide more effective outcomes. Potential strategies include treatments aimed at rebalancing T and B cell activity, developing vaccines, or tailoring therapies to individuals with specific genetic risk factors.

The authors stress that much remains to be understood. Researchers are still working to clarify how immune cells enter the brain, why they act differently in different patients, and how age-related immune changes intersect with Alzheimer’s. These questions will be crucial for designing precise diagnostics and effective therapies.

“Adaptive immunity has moved from being a side note to being recognized as a key player in AD,” Dr. Chen adds. “We are only beginning to grasp its complexity, but this line of research may help transform the way we prevent and treat the disease.”

Overall, this review highlights the growing consensus that Alzheimer’s is not only a disorder of plaques and tangles but also a disease of immune imbalance. As the burden of Alzheimer’s continues to rise worldwide, understanding and harnessing the immune system may open new avenues for prevention and treatment, offering hope to patients, families, and healthcare systems.

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Reference

DOI: http://doi.org/10.1097/cm9.0000000000003695