What is it about?
Killer T cells are known to be different in Alzheimer's disease, but their role in disease initiation and progression is controversial. We have shown for the first time that aged killer T cells enter brain and initiate signs and symptoms of Alzheimer's. T cells had only ever been examined after Alzheimer's signs and symptoms started, and their differences in afflicted patients were widely assumed to be an effect of disease initiation. By contrast, we showed that they are a potential cause.
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Why is it important?
There is no known cause for non-inherited forms of Alzheimer's, other than age. We recreated one of the earliest manifestations of human aging in mice - accumulation of abnormal killer T cells in blood - and systematically showed that this factor not only initiates signs and symptoms of Alzheimer's in mice, but blocking the T cells' function decreased or eliminated those disease features, and that similar T cells were altered in human Alzheimer's patients. We used knowledge of these T cells to predict previously unknown features of human Alzheimer's, and showed that quantifying particular T cells can be useful as a diagnostic tool for the disease.
Perspectives
My mother developed Alzheimer's in her mid-50s, while I was a postdoctoral fellow in Immunology. I decided to apply my training to brain diseases, in part due to this personal connection. When my lab created an animal model of aging T cells, my immediate hope was that it could be used to improve brain tumor immunotherapy, but when we noticed abnormalities consistent with Alzheimer's, the focus was changed. I am so thankful I was able to ultimately attract an enormously talented group of collaborators, who together added substantial strength to this new focus. I dedicate this paper as an outcome of our collective work to my dear mother and father (her main caregiver), her beloved cousin and all others impacted by Alzheimer's disease and dementia.
Dr. Christopher J. Wheeler
T-Neuro Pharma
Read the Original
This page is a summary of: Antigen-specific age-related memory CD8 T cells induce and track Alzheimer’s-like neurodegeneration, Proceedings of the National Academy of Sciences, July 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2401420121.
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