A gene which protects against cancer is linked to an increased risk of Alzheimer’s disease, scientists have found, suggesting that there may be a trade-off in the conditions.

Scientists have found 75 genes associated with a heightened chance of developing Alzheimer’s, including 42 new genes which had not previously been implicated in the condition.

Among them is the gene responsible for the TNF-alpha (tumour necrosis factor) signalling pathway, which plays an important role in inflammation and the immune system, and helps keep cancer at bay.

Although researchers are unclear how TNF-alpha causes harm in the brain, they believe it could cause the over-activation of immune cells called microglia, which may “eat” the synapses, the junctions between neurons.

Laboratory studies have also previously shown that blocking TNF-alpha signalling can reduce the sticky amyloid plaques and tau tangles which are present in Alzheimer’s.

‘An interesting hypothesis to explore’

Prof Jean-Charles Lambert, the research director of Inserm, the French national institute of health and medical research, said: “Many epidemiological data seem to indicate an inverse correlation between the risk of having cancer and the risk of dementia.

“This suggests that these pathologies may share common mechanisms, but with opposite effects. We don’t know how the TNF-alpha pathway could play out at this level, but it’s an interesting hypothesis to explore.”

Previous research has found that cancer patients have a 35 per cent lower risk of developing Alzheimer’s, while Alzheimer’s patients have about half the risk of getting cancer compared to the general population.

Prof Lambert said: “There is no longer any doubt that the genetics of the common forms of Alzheimer’s disease point to the involvement of the immune system and an inflammatory response.

“Our work confirms this by indicating the important role of microglia. Microglia may be protective, but it is also possible that the activation of microglia is deleterious.

“The implication [of TNF-Alpha] in the control of neuroinflammation and potentially microglia activation is of particular relevance in Alzheimer’s disease, and may clearly lead to understanding the role of these cells.”

Focus turns toward new treatments

Alzheimer’s disease is the most common cause of dementia, a condition that affects more than 850,000 people in Britain.

In the largest study of its kind, researchers from the UK, US, Australia and Europe analysed the genomes of more than 100,000 people with the condition and compared them with more than 600,000 healthy individuals to look for differences in their genetic make-up.

Now that target genes have been identified, researchers can focus on what role they are playing in damaging brain cells so that new treatments can be found.

Prof Julie Williams, the director of Cardiff University’s dementia research institute, and the co-author of the study, said: “The results support our growing knowledge that Alzheimer’s disease is an extremely complex condition, with multiple triggers, biological pathways and cell types involved in its development.

“We are unmasking more of these causes year on year, and this also provides greater opportunities from which to develop therapeutics.

“Components of our immune system have a big role to play in the development of the disease. For example, immune cells in the brain known as microglia are responsible for clearing out damaged tissue, but in some people that may be less efficient, which could accelerate the disease.”

Genetic risk score

Researchers have also devised a genetic risk score to determine how likely patients with cognitive impairment will, within three years of first showing symptoms, go on to develop Alzheimer’s disease.

The score is not intended for use in clinical practice at present, but researchers hope it will improve the evaluation of new drugs in clinical trials.

Dr Rebecca Sims, the co-leader of the study and a co-investigator at the UK Dementia Research Institute, said: “This study more than doubles the number of identified genes influencing risk for the more common form of Alzheimer’s disease.

“It provides exciting new targets for therapeutic intervention and advances our ability to develop algorithms to predict who will develop Alzheimer’s in later life.”

The research was published in the journal Nature Genetics.