Can Alzheimer’s be caused by viral infection? Decoding research on a new risk factor

Why do scientists think that viral infections may cause Alzheimer’s?

While researchers are yet to pinpoint what causes Alzheimer’s disease, over the years there has been enough evidence to suspect that certain infections might have a role to play. Researchers have hypothesised that an inflammation in the brain triggers the abnormal build-up of amyloid beta and tau proteins, one of the reasons for which is infection.

They have found linkages to support their theory — researchers have found genetic material of the HSV-1 in these amyloid plaques. A 2022 study found that repeated head injuries can reawaken a dormant HSV-1 infection. Concussions and brain injuries are known risk factors for Alzheimer’s disease. A shingles infection can also reactivate the HSV-1 virus — this could be the reason scientists have found that the incidence of Alzheimer’s is lower in people who have been vaccinated against it.

Alzheimer’s: How viruses can be a trigger

A recently published large “natural experiment” — based on health data of 280,000 older individuals from Wales — found that the people who had been vaccinated were 20% less likely to develop dementia. Alzheimer’s is one of the most common forms of dementia.

“The exact cause of dementia is not known. However, there are several triggers that have been liked to it such as repeated head injuries, viral infections, living with conditions such as blood pressure, diabetes, sleep disorders like obstructive sleep apnoea, and insomnia,” says Dr Tripathi. Among them the viral hypothesis is very strong because it has been shown that these viral infections could “trigger the pathological hallmarks of the dementia like amyloid plaque formation.” Some scientists argue that it may not be the infection per se but the body’s response to it that could be the culprit.

Researchers see abnormal protein clumps seen in the brains of patients with Alzheimer’s as a defence mechanism, to protect the brain from pathogens. Scientists in 2018 were able to demonstrate in brain cells and mice in the laboratory that a viral infection triggered the protein plaque formation as a trap for the microbes. While young people have the ability to clear out these plaques efficiently, it is not so with older persons, leading to Alzheimer’s. There is also some evidence to suggest that vaccines other than shingles — such as influenza and tuberculosis — could also lower the incidence of Alzheimer’s.

Why is the viral infection theory in focus?

If infections are the likely trigger of Alzheimer’s, then the onset may be prevented through vaccination. “While we may not have all the answers yet, it would be good to get vaccinated with all available vaccines. It is a common misconception that vaccines have to be taken only in childhood — adults should be taking the flu, pneumonia and shingles vaccines,” says Dr Tripathi.

What about research on other triggers of Alzheimer’s?

Researchers are looking at the gut-brain axis hypothesis that suggests changes in the gut microbiome make the intestine more permeable. This is the blood brain barrier that does not allow several molecules to reach the brain. Once damaged, they go through and result in brain inflammation.

Another hypothesis suggests that autophagy, or the process by which cells dispose damaged parts — in this case abnormal amyloid beta protein and tau protein — gets affected. The metal-ion hypothesis suggests that increased cell damage in the brain is what leads to Alzheimer’s disease.

What are currently available therapies for Alzheimer’s?

At least three therapies for Alzheimer’s have been approved by the US Food and Drug Administration — all working on the principle of a monoclonal antibody removing the abnormally clumped proteins from the brain of patients. While these drugs cannot reverse memory loss, they can slow the progression of the disease. The phase III study for the most recently approved donanemab found that cognitive decline slows down in early Alzheimer’s patients by 35.1% at 76 weeks. These drugs, however, are known to cause small bleeds in the brain.

“There are new therapies that have come out in the market but these are terribly expensive. What we need now are cheaper therapies that can prevent the disease,” says Dr Tripathi.