Stimulating Toll-Like Receptor 9 Eases Alzheimer's Disease in Mouse Model

A method for stimulating the immune response of the nervous system reduces the amount of toxic amyloid plaque in the brains of a mouse model of Alzheimer's disease.

Investigators from the New York University School of Medicine (New York City, USA) worked with the Tg2576 transgenic mouse line, a model system for human Alzheimer's disease (AD). They injected a group of these animals with cytosine-guanosine containing DNA oligodeoxynucleotides (CpG ODNs), a procedure designed to stimulate the innate immune system via the Toll-like 9 receptor (TLR9). After 17 months the animals were compared to untreated AD mice for amyloid plaque burden and to both AD and normal mice for ability to navigate a maze.

Results published in the February 11, 2009, online edition of The Journal of Neuroscience revealed that CpG ODN treatment produced a 66% and 80% reduction in the cortical and vascular amyloid burden, respectively, compared with untreated AD mice. The treated AD mice performed similarly to wild-type mice on a radial arm maze while the untreated AD group performed poorly. No signs of toxicity were found in the mice that received the CpG ODN treatment.

"Our results indicate that stimulation of the innate immune system through TLR9 with CpG ODNs is an effective and apparently non-toxic method to reduce the amyloid burden in the brain,” said senior author Dr. Thomas Wisniewski, professor of neurology, pathology, and psychiatry at the New York University School of Medicine. "Furthermore, we found that amyloid reduction was associated with significant cognitive benefits in an AD mouse model. This approach has significant implications for future human immunomodulatory approaches to prevent AD in humans.”

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New York University School of Medicine