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Immunotherapy Against Tau Tangles in Alzheimer's

Posted Jul 15 2009 6:56pm


"We believe that these results point to the therapeutic potential of phosphorylated-tau-immunotherapy in Alzheimer's," Rosenmann said. "We devoted significant effort to address not only the anti-tangle effect but also safety of a phosphorylated-tau vaccine. This was done in order to identify early in the preclinical stage any potential hazard of this potential Alzheimer's therapy."
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Immunotherapy Against Tau Tangles in Alzheimer's Mouse Models

Immunotherapy (treatment by inducing, enhancing, or suppressing an immune response) targeting beta amyloid is being researched widely by companies and academics as a therapeutic option for Alzheimer's disease. Earlier, late stage, anti-amyloid immunotherapy trials in people were complicated, and eventually stopped, when about six percent of participants developed brain inflammation. Current trials in this area are working in a variety of ways to eliminate this side effect.

Tau tangles, the other major Alzheimer's brain pathology, are now also receiving attention as a target for immunotherapy. Also known as neurofibrillary tangles (NFTs), these lesions consist of an abnormal folded protein (phosphorylated tau), and research shows their accumulation in the brain is more closely associated with the progression of Alzheimer's symptoms than amyloid.

Building on previous studies using this approach (for example, Asuni et al. (2007)), Hanna Rosenmann, Ph.D., head of the Laboratory of Molecular Neurogenetics, Department of Neurology, Hadassah University Hospital, Ein Kerem, and an Investigator (Associate-Senior Lecturer) at the Hebrew University Hadassah School of Medicine, Jerusalem, Israel, and colleagues performed immunization studies against tau tangle pathology by immunizing NFT mice with a mixture of three phosphorylated-tau peptides (shortened versions of the full length tau protein that are phosphorylated like the NFTs). Previous experiments by this lab with non-phosphorylated full length tau caused brain inflammation in the animal models.

The researchers observed a robust decrease in the number of tau tangles in the brains of the mice immunized with the phosphorylated tau-peptides (~40%; p <0.001), and detected anti-phosphorylated-tau antibodies in mouse serum. They found no evidence or symptoms of brain inflammation in the immunized mice.

According to Rosenmann, the decrease in tau tangles observed by her team is in accord with previous findings by Asuni's group, though Asuni immunized with a different phosphorylated tau peptide and immunization protocol.

"We believe that these results point to the therapeutic potential of phosphorylated-tau-immunotherapy in Alzheimer's," Rosenmann said. "We devoted significant effort to address not only the anti-tangle effect but also safety of a phosphorylated-tau vaccine. This was done in order to identify early in the preclinical stage any potential hazard of this potential Alzheimer's therapy."

Moran Boimel, et al -- Immunotherapy Targeting Pathologically Phosphorylated Tau In A Tauopathy Mouse Model (Funder: Agnes Ginges Fund)

About ICAD 2009
The 2009 Alzheimer's Association International Conference on Alzheimer's Disease (ICAD 2009) brings together more than 5,000 researchers from 60 countries to share groundbreaking research and information on the cause, diagnosis, treatment and prevention of Alzheimer's disease and related disorders. As a part of the Association's research program, ICAD 2009 serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community. ICAD 2009 will be held in Vienna, Austria at Messe Wien Exhibition and Congress Center from July 11–16.

About the Alzheimer's Association
The Alzheimer's Association is the leading voluntary health organization in Alzheimer care, support and research. Our mission is to eliminate Alzheimer's disease through the advancement of research, to provide and enhance care and support for all affected, and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer's. For more information, visit www.alz.org.
Bob DeMarco is an Alzheimer's caregiver and editor of the Alzheimer's Reading Room. The Alzheimer's Reading Room is the number one website on the Internet for advice and insight into Alzheimer's disease. Bob taught at the University of Georgia, was an executive at Bear Stearns, the CEO of IP Group, and is a mentor. He has written more than 700 articles with more than 18,000 links on the Internet. Bob resides in Delray Beach, FL.

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