CpG DNA Therapy For Alzheimer Disease

ScienceDaily (Oct. 22, 2009) — Dr. Yukiko Doi and colleagues at Nagoya University have found that CpG DNA may be a therapeutic candidate for treatment of Alzheimer disease. They report their data in the November 2009 issue of The American Journal of Pathology.

Alzheimer disease is the most common form of dementia, affecting approximately 1.6% of the population in the United States (nearly 19% in the 75-84 age group). It is an incurable, degenerate, and terminal disease thought to be caused by accumulation of oligomeric amyloid ? (??oA?).

Microglia are the resident immune cells in the central nervous system; they remove damaged neurons, plaques, and infectious agents from the brain and spinal cord. Microglia cluster around senile A??plaques in Alzheimer disease patients; however, the role of microglia in oA??toxicity remains unclear. Doi et al discovered that microglial activation with unmethylated CpG DNA, which binds to an immune receptor on microglia, prevented oA??toxicity and enhanced oA? ?peptide clearance in culture. Furthermore, injection of CpG DNA directly into the brain mitigated both cognitive impairment and learning defects in a mouse model of Alzheimer disease. CpG DNA may therefore be a therapeutic candidate for treatment of Alzheimer disease.

Dr. Doi and colleagues conclude that “CpG, especially class B and C, may also be effective therapeutic agents against oA?1-42 ?neurotoxicity in [Alzheimer disease].”

1. Doi Y, Mizuno T, Maki Y, Jin S, Mizoguchi H, Ikeyama M, Doi M, Michikawa M, Takeuchi H, Suzumura A. Microglia Activated with the Toll-Like Receptor 9 Ligand CpG Attenuate Oligomeric Amyloid ? Neurotoxicity in in Vitro and in Vivo Models of Alzheimer’s Disease. American Journal Of Pathology, 2009; DOI: 10.2353/ajpath.2009.090418