11th September 2023,Mumbai: Alzheimer’s disease, affecting up to 5.8 million Americans, remains a relentless foe that robs individuals of their cognitive abilities, particularly memory. Among the hallmarks of this devastating neurological ailment are beta-amyloid plaques, protein clumps that wreak havoc in the brain. Recent research from St. Jude Children’s Research Hospital reveals a promising avenue in the battle against Alzheimer’s, highlighting the role of T cells in interacting with microglia, the brain’s immunological cells responsible for clearing beta-amyloid plaques. This discovery, published in Nature Immunology, sheds light on how T cells could potentially slow down the progression of Alzheimer’s.
The Immune System’s Enigmatic Role in Alzheimer’s
While we traditionally associate the immune system with defending against bacterial and viral infections, there is growing intrigue surrounding its involvement in neurodegenerative diseases like Alzheimer’s. St. Jude’s co-first author, Jordy Saravia, Ph.D., emphasizes this emerging dimension: “We uncovered an important immune cell communication axis that is protective in an Alzheimer’s disease model.” Microglia, typically tasked with removing beta-amyloid plaques, may lose their efficacy as Alzheimer’s advances, potentially contributing to plaque formation. However, the researchers at St. Jude discovered that a specific type of immune cell, CD8 T cells, plays a crucial role in maintaining the balance, preserving cognitive function in a mouse model of the disease.
A Novel Protective Role for CD8 T Cells
The groundbreaking aspect of this study lies in its revelation that a subpopulation of CD8 T cells can provide protection against Alzheimer’s disease progression. Wei Su, Ph.D., co-first author, notes, “Moving forward, we may be able to extend this work to find an effective intervention for neurodegenerative diseases.” Prior research had offered complex perspectives on the roles of T cells in Alzheimer’s, with some indicating that certain T cells with inflammatory functions exacerbate the disease. However, the St. Jude scientists spotlighted the significance of CD8 T cells with suppressive attributes, underscoring the intricate interplay between T cells and Alzheimer’s.
A Handshake between Cells: Unraveling the Mechanism
To comprehend how T cells delay Alzheimer’s symptoms, the St. Jude team sought the most abundant molecular interaction between CD8 T cells and microglia. They uncovered a protein on CD8 T cells, CXCR6, that interacts with CXCL16, a protein expressed by microglia. This interaction, akin to a handshake between cells, facilitates bidirectional communication. Just as the firmness of a human handshake can convey meaning, the interaction of CXCR6 and CXCL16 on cell surfaces carries vital information.
The Handshake’s Role In Disease Mitigation
The CD8 T cells’ handshake with microglia emerges as a critical factor in slowing the progression of Alzheimer’s. First, CD8 T cells move close to the microglia situated near beta-amyloid plaques. Then, they employ the handshake to signal to microglia to curtail excessive inflammation, thereby impeding plaque growth and symptom development in mouse models. When the gene responsible for CXCR6 in CD8 T cells was deleted, mice experienced more severe Alzheimer’s symptoms. This result stemmed from CD8 T cells without CXCR6 failing to accumulate in the brain near microglia or plaque sites, and they lost their suppressive function. Essentially, disrupting the CD8 T cells’ ability to perform the handshake negated their protective effect against Alzheimer’s symptoms.
Two Key Findings and a Path Forward
In summary, the study from St. Jude presents two significant findings. First, CD8 T cells play a pivotal role in maintaining brain homeostasis, offering protection against Alzheimer’s disease-related disruptions. Second, the T cell protein CXCR6 emerges as central to CD8 T-cell accumulation and function in the brain. These discoveries underscore the need for a deeper understanding of neuro-immune interactions to advance the field and develop novel treatments for neurodegenerative diseases like Alzheimer’s. While the battle against Alzheimer’s remains arduous, these findings offer renewed hope in the form of T cells’ potential to slow the disease’s progression and preserve cognitive abilities.
-by Kashvi Gala