Alzheimer’s diseaseFungus, the bogeyman

LIKE cancers and heart disease, Alzheimer’s is a sickness of the wealthy. That is because it is a sickness of the old. A study carried out in Spain in 2008 suggested that the risk of developing it doubles for every five years you live beyond 65. A richer world means a longer-lived world—and that, in turn, means a world which will suffer more and more from dementia. At least 40m people are thought to be affected by it already. The true number is likely to be higher, as many sufferers, particularly in the early stages of the disease, have yet to be diagnosed.

What actually causes Alzheimer’s disease, though, is obscure. Workers in the field know that tangles and plaques of misshapen proteins play a big role. These accumulate in and between nerve cells, eventually killing them to create voids in the brain (see picture). It may be that the accumulation of these proteins is merely a biochemical ill to which human flesh is unfortunately heir, and which is a normal (if unwelcome) consequence of ageing. But some researchers doubt that, and are searching for external causes. There is evidence, in varying degrees, for everything from bacterial or viral infections, via head injuries to smoking. But a paper just published in Scientific Reports adds another possibility to the pot. A group of researchers led by Luis Carrasco of the Autonomous University of Madrid, in Spain, have raised the idea that the ultimate cause of Alzheimer’s is fungal.

Dr Carrasco and his team examined brain tissue from 25 cadavers, 14 of which belonged to people who had had Alzheimer’s disease when alive. The other 11 (who had an average age of 61, versus 82 for the Alzheimer’s sufferers) had been Alzheimer’s-free. That may sound like a small sample from which to draw conclusions, but the signal the researchers found was overwhelming. Every single one of the Alzheimer’s patients had signs of fungal cells of various sorts growing in his or her neurons. None of the Alzheimer’s-free brains was infected.

Assuming Dr Carrasco and his team have made no methodological errors (and there is no suggestion that they have), then the question is one of causation. Do fungi usher in the disease, or does the disease usher in the fungi? An observational study like this cannot answer that question. But Dr Carrasco and his colleagues point out that what is known about Alzheimer’s fits with what is known about fungal infections. Alzheimer’s progresses slowly, as do untreated fungal infections. Alzheimer’s patients exhibit signs of inflammation and an aroused immune system, which fungal infection might be expected to trigger. And the damaged blood vessels observed in many people with Alzheimer’s fit with Dr Carrasco’s observation of fungus growing in these vessels.

If fungal infection did turn out to be responsible for Alzheimer’s, that would be excellent news. Medicine already possesses plenty of anti-fungal medications that could be raided to produce anti-Alzheimer’s drugs. But Dr Carrasco’s evidence, while intriguing, is far from conclusive. John Hardy, a neuroscientist at University College, London, points out that one (albeit rare) cause of Alzheimer’s is well-understood. In a few unlucky families the disease appears to be an inherited disorder, caused by mutations of one of three genes. If a fungal infection were the ultimate cause, then those genetic mutations would have to make their carriers so susceptible that 100% of them end up infected, something he believes is unlikely. And the very clarity of Dr Carrasco’s result also makes Dr Hardy suspicious.

If that result is right, though, it is still possible that the correlation runs the other way, with Alzheimer’s opening the brain to fungal infection. After all, says Ian Le Guillou of the Alzheimer’s Society, a British charity, the disease is thought to damage the blood-brain barrier, an immunological shield which keeps the brain safe from pathogens and toxins. The presence of fungi might merely reflect a greater susceptibility to infection.

Dr Carrasco and his team think a clinical trial of anti-fungal drugs is the next logical step. But there is yet another possibility. In the absence of a definitive ultimate cause, it may be that the symptoms of Alzheimer’s disease can arise from many different types of insult to the brain. There have been several papers, says Dr Le Guillou, that have found correlations between various infectious organisms and Alzheimer’s. “It could be a bit like the Mississippi river,” says Dr Hardy. “You can start in all sorts of places, but eventually you’re going to end up in New Orleans.” If Alzheimer’s is a general response to all sorts of neurological triggers then it may be that the fungal infections found by Dr Carrasco are simply one of a long list of causes.