Researchers at NYU Langone Medical Center have discovered a novel way to stimulate the innate immune system of mice with Alzheimer's disease (AD) - leading to reduced amyloid deposits and the prevention of Alzheimer's disease related pathology - without causing toxic side effects.
The study entitled "Induction of Toll-like Receptor 9 Signaling as a Method for Ameliorating Alzheimer's Disease Related Pathology" was published in The Journal of Neuroscience.
NYU Langone researchers stimulated the innate immune system via the Toll-like 9 receptor (TLR9) via treatment with cytosine-guanosine containing DNA oligodeoxynucleotides (CpG ODNs) in Tg2576 AD model transgenic mice. This treatment produced a 66% and 80% reduction in the cortical and vascular amyloid burden, when compared with non-treated AD mice. Also, vaccinated Tg2576 mice performed similarly to non-treated mice on a radial arm maze used in the study, showing improvements in behavior and reduced amyloid burden.
"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 Thomas Wisniewski, MD, professor of neurology, pathology and psychiatry at NYU Langone Medical Center. "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."
The deposition of amyloid â (Aâ) in the central nervous system in the form of amyloid plaques is a hallmark of Alzheimer's disease. Aâ accumulation destroys neurons in the brain, leading to deficits in cognitive abilities. Immunomodulation or vaccination for AD is emerging as an effective means of shifting the equilibrium from Aâ accumulation to clearance; however, excessive cell mediated inflammation and cerebral microhemorrhages - two forms of toxicity- were shown to occur in previous vaccination studies targeting the adaptive immune system.
"This innate immune approach did not have any of the problems previously reported with immunomodulation targeting the adaptive immune system, such as encephalitis, hemorrhages or lack of an effect on vascular amyloid, suggesting that this method has significant advantages," said Dr. Wisniewski "The treatment with CpG ODNs has already been tested in normal human volunteers and found to be safe- in studies where CpG ODNs was to be used to treat chronic infections; hence this AD treatment has the potential to be brought to clinical trial relatively quickly."