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Neurofibrillary tangles (tangles) are one of the two primary brain lesions found in AD and are probably involved in neuronal cell death. Tangles are formed following conversion of a normal brain protein called tau (normal tau) to abnormal tau (contain high levels of a chemical called phosphate) which is toxic to brain cells. Drugs aimed at preventing formation of abnormal tau and tangles may be useful in treating AD. Dr. Iqbal and his colleagues plan to develop two high throughput-screening assays to screen for compounds with anti-tangle activity: The first assay will identify compounds that prevent normal tau becoming abnormal tau by blocking the addition of phosphates. The second assay will identify compounds that block abnormal tau from converting normal tau into abnormal tau through a chain reaction. It is planned to make the assays commercially available to screen for new anti-tangle compounds.