Tau phosphorylation and Alzheimer's disease
Published 13 November 2007
Tau protein forms the tangles that are one of the two recognisable features of Alzheimer’s disease morphology (the other being the amyloid plaques).
Phosphorylation and dephosphorylation are part of the normal processing tau undergoes in the healthy nerve cell in the brain. Tau protein can form the tangles that are observed in the brain of people with Alzheimer's disease following overproduction or over-phosphorylation. It has long been discussed whether the tangles are a secondary feature of the development of the disease or part of what causes the nerve cells to die.
Professor Lu has identified an enzyme (Pin1), present in all types of cells, that assists in dephosphorylating tau. He and his colleagues have demonstrated a link between a decreased amount of this enzyme and the presence of tangles in post-mortem brain material from people with Alzheimer's disease. In order to further investigate the action of Pin1, Prof Lu developed a mouse strain engineered to not produce the Pin1 enzyme. These mice went on to develop Alzheimer's disease-like symptoms, age related tangles and neuronal cell death.
These results are very exciting because they provide the first mouse model for Alzheimer's disease that represent an under expression of a gene. It also supports the idea that over-phosphorylation of tau is an early event in the development of Alzheimer's disease.
Alzheimer's disease is likely to be a multi-factorial disease with the involvement of more than one gene and disease causing mechanism. More research is needed to work out the mechanism for this particular enzyme's action and to identify therapeutic targets.
This type of basic research on the causes of Alzheimer's disease is very important. It provides hope for people with Alzheimer's disease and their families that in the future it will be possible to treat the disease in earlier stages than is presently possible.