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Alzheimer's disease

The tangled tale of tau

Nature volume 402, pages 588–589 (1999)Cite this article

Alzheimer's disease is the main form of dementia in today's ageing population. It is characterized by abnormal protein deposits in the brain, such as the extracellular amyloid plaques and the intracellular neurofibrillary tangles. The tangles are made up of a protein called tau, which is modified by phosphorylation and aggregated into so-called paired helical filaments. Because hyperphosphorylation seems to occur before aggregation, it is considered one of the earliest signs of neuronal degeneration. But which protein kinases are responsible for it?

Two papers in this issue go some way towards answering this question. Tsai and colleagues1 (page 615) report that the cyclin-dependent kinase 5 (Cdk5) is deregulated in the brains of people with Alzheimer's disease. Not only that, but Cdk5 also hyperphosphorylates tau and accumulates in tangle-bearing neurons. And Greengard and colleagues2 (page 669) show that Cdk5 can alter signalling processes in neurons by altering the balance between its kinase and phosphatase activities.

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Figure 1: Hyperphosphorylation and aggregation of tau.
Figure 2: Regulation of the cyclin-dependent kinase 5 (Cdk5).

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  1. the Max-Planck-Unit for Structural Molecular Biology, Notkestrasse 85, Hamburg, D22607, Germany

    E. Mandelkow

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Mandelkow, E. The tangled tale of tau. Nature 402, 588–589 (1999). https://doi.org/10.1038/45095

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