STUDIES of a protein called tau are bringing scientists closer to understanding Alzheimer鈥檚 disease.
Claude Wischik of the Cambridge Brain Bank Laboratory has investigated the properties of tau, which in its abnormal state forms insoluble tangles in the brain cells of Alzheimer鈥檚 patients. Last week he told an international symposium in Cambridge that the abnormal, tangle-forming protein can convert normal tau to the abnormal form.
Alzheimer鈥檚 disease manifests itself in the brain in two ways. As well as the tau tangles, sufferers鈥� brains contain plaques of a protein called amyloid. But scientists do not know whether either the tangles or the plaques cause dementia.
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Wischik decided to see whether there was a correlation between the severity of the disease and the quantity of tau tangles in the brain. He looked at the brains of patients who had been suffering from Alzheimer鈥檚 when they died, and compared them with the brains of people who died mentally normal. The number of tangles in the brain correlated well with the extent of the patients鈥� dementia. Wischik also found that the proportion of normal tau fell from 97 per cent in the normal patients to 17 per cent in those with severe Alzheimer鈥檚.
Normal tau helps maintain microtubules, which form the 鈥渟keleton鈥� that gives nerve fibres their shape. Wischik suspected that in Alzheimer鈥檚 patients the normal protein is converted into the abnormal form. So he took the abnormal protein, which is shorter than the normal version, and mixed it in a test tube with normal tau and enzymes found in nerve cells which digest proteins.
He found that the abnormal protein bound very strongly to normal tau. The enzymes were unable to break down the abnormal tau, but they cut the ends off normal protein molecules which had bound to abnormal tau, converting them to the abnormal form. These in turn became 鈥渕agnets鈥� to which other normal tau molecules bound. 鈥淵ou can鈥檛 break out of it once it starts,鈥� says Wischik. The abnormal tau gradually clumps together to make the tangles. Wischik is uncertain what starts the process, but he says there may be many triggers, both genetic and environmental.
If the same process occurs in the body, and the tangles do cause dementia, slowing the conversion of tau to the abnormal form could slow the progress of the disease. Wischik has identified four compounds which can stop tau binding to itself. He now intends to test these compounds in cultured nerve cells.