• Scientists have misunderstood Alzheimer’s disease for 30 years
  • Study now believes beta-amyloid protein – a hallmark of the disease – may accumulate in the brain after fighting infection 
  • Discovered beta-amyloid protein protected against lethal infections
  • Mice, genetically engineered to produce the protein, survived significantly longer after their brains were infected by salmonella than normal mice 

It is the most common form of dementia, and yet there is still no means of preventing or curing Alzheimer’s disease. A new study suggests the reason, in part, is that scientists have misunderstood the condition for years. Scientists believe the notorious protein that is a hallmark of Alzheimer’s disease may play a key role in fighting infection. Beta-amyloid forms sticky clumps, or ‘plaques’, in the brain, a sign that is used to diagnose the condition.

But the new findings provide strong evidence that beta-amyloid is also part of the innate immune system, the body’s first line of defence against bacteria, viruses and parasites. Scientists found that human beta-amyloid (A-beta) protected against lethal infections in mice, laboratory worms and cultured human brain cells.

Dr Robert Moir, from Massachusetts General Hospital, said: ‘Neurodegeneration in Alzheimer’s disease has been thought to be caused by the abnormal behaviour of A-beta molecules, which are known to gather into tough fibril-like structures called amyloid plaques within patients’ brains. This widely held view has guided therapeutic strategies and drug development for more than 30 years, but our findings suggest that this view is incomplete.’

Previous research co-led by Dr Moir showed that beta-amyloid from the brains of Alzheimer’s patients suppressed the growth of Candida yeast, a common fungal infectious agent, in the laboratory. The new study is the first to investigate the anti-microbial action of human beta-amyloid in living animals. Mice genetically engineered to produce the protein survived significantly longer after their brains were infected by salmonella than normal mice.

Beta-amyloid forms sticky clumps, or ‘plaques’, in the brain, a sign that is used to diagnose the condition

Roundworms that generated A-beta were also protected against Candida and Salmonella. In addition, the protein prevented Candida from infecting cultured neuronal cells. A-beta generated by living cells appeared to be 1,000 times more protective than a synthetic version of the molecule. In fact it could be one of the properties of ‘natural’ A-beta associated with Alzheimer’s – its ability to aggregate into plaques – that might be responsible for its contribution to immunity. A fundamental process involves the clumping together of small molecules that prevents infectious agents from attaching to host cells. The clumping is also thought to kill microbes by disrupting their cellular membranes.

Dr Moir said: ‘Our findings raise the intriguing possibility that Alzheimer’s pathology may arise when the brain perceives itself to be under attack from invading pathogens, although further study will be required to determine whether or not a bona fide infection is involved. It does appear likely that the inflammatory pathways of the innate immune system could be potential treatment targets. If validated, our data also warrant the need for caution with therapies aimed at totally removing beta-amyloid plaques. Amyloid-based therapies aimed at dialling down but not wiping out beta-amyloid in the brain might be a better strategy.’

The research is published in the journal Science Translational Medicine. 

Source: DailyMail