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2011 Grants - Adlard
Metals and Neurofibrillary Tangles: A Novel Therapeutic Target
Paul A. Adlard, Ph.D
Mental Health Research Institute
2011 New Investigator Research Grant
Numerous scientific studies have focused on the role of metals in the development of amyloid plaques, one of the characteristic features of Alzheimer's pathology or brain changes. Recent studies have found evidence that metals may be involved in the development of neurofibrillary tangles, the other characteristic feature of Alzheimer's pathology or brain changes.
Neurofibrillary tangles are formed from the protein tau, which is normally an important part of nerve cell structure and which participates in the transport of nutrients throughout the cell. Recent evidence supports the idea that metals may interact with tau, possibly leading to the formation of neurofibrillary tangles.
Paul A. Adlard, Ph.D. and colleagues have proposed two-pronged research studies to examine the interactions between tau and metal ions in the brains of mice. The researchers will use two different strains of mice, one in which the gene for tau has been removed, and another in which mutant tau is overexpressed. Using each of these models, they will analyze the interactions of tau with metal ions at different ages. Dr. Adlard and colleagues will also use drugs known to alter the distribution of metals in the brain and determine if such drugs affect interactions between tau and metals in both animal models. These studies will address important questions about the role of metal ions in the development and formation of neurofibrillary tangles, and potentially identify new targets for treatments to inhibit their formation.