9 May 2005: Scientists tangle over tau

The aggregations of tangled nerves in patients with neurodegenerative disease could be good rather than bad news, argue scientists in the US. This challenges the conventional wisdom that so-called neurofibrillary tangles (NFTs) play a key role in the progression of neurodegenerative conditions.

NFTs are one of the major features seen in the brains of patients with neurodegenerative diseases like Alzheimer’s disease (AD). These tangles, which contain aggregations of a phosphorylated protein called tau, are so characteristic of such diseases that they have become collectively known as ’tauopathies’.

However, this need not necessarily mean that NFTs are causing the disease, says Mark Smith, a pathologist at Case Western Reserve University in Cleveland, Ohio. There is growing evidence that oxidative stress is a significant factor in the development of AD, he says. ’Since oxidative stress is decreased in neurons bearing NFTs, we suspect that the accumulation of tau proteins might actually be a protective, antioxidant repsonse that serves as a mechanism for cells to defend themselves.’

It is possible that aggregate formation may be a protective response, says John Trojanowski, director of the Alzheimer’s Disease Center at the University of Pennsylvania School of Medicine. But even if this turns out to be the case, aggregates soon become more harmful than beneficial, he says. ’The relentless accumulation of aggregates in neurons and their processes are, on balance, more deleterious than protective over time.’

Nevertheless, Smith’s team argues that the idea has ’broad implications for both the understanding of mechanisms underlying disease pathophysiology and the design of new therapeutic strategies.’

Henry Nicholls