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2010 Grants - Wisniewski
Immunotherapy for Amyloid Plaques, CAA and Neurofibrillary Tangle Pathology
Thomas Wisniewski, M.D.
New York University School of Medicine
New York, New York
2010 Investigator-Initiated Research Grant
One theme common to several neurodegenerative pathologies is the central role of a misfolded protein or protein fragment. For example, Alzheimer's disease and cerebral amyloid angiopathy (CAA) involve misfolding and abnormal aggregation of the protein fragment beta-amyloid or the protein tau, or both. None of these pathologies or neurogenenerative disorders have effective treatments, although clinical trials are underway. One approach being studied in clinical trials involves stimulation of the immune system to recognize the abnormal protein. To date, these treatment have had limited success and caused significant side effects.
Thomas Wisniewski, M.D., and colleagues are working to develop more effective strategies for using the immune system to remove protein fragments associated with the formation of amyloid plaques. The researchers are using a protein fragment known as ABri, which forms amyloid plaques in persons with a rare form of dementia known as inherited British dementia. Like beta-amyloid, the protein fragment implicated in Alzheimer's disease, ABri aggregates into clusters known as oligomers.
Dr. Wisniewski's team has found that immunization of animals using aggregated ABri stimulates the immune system to recognize aggregated beta-amyloid. This approach may allow the immune system to remove aggregated beta-amyloid from the brain without disturbing normal, unaggregated beta-amyloid. The researchers now plan to extend their studies to determine if immunization using ABri removes beta-amyloid from the brains of mice with Alzheimer-like pathology, or from the blood vessels of mice with a disease similar to CAA. They will monitor changes in brain pathology as well as changes in cognitive function to determine if the immunization is successful. These studies will provide initial evidence about the safety and effectiveness of a new immunization strategy and whether that strategy should be developed for further study.