An epidemiologist’s perspective on an association between Alzheimer’s and its possible role in the detection of herpesviruses and shingles

Some studies have been done since Warren-GASH and her colleagues reviewed the links between active viral infections and Alzheimer’s. For example, Nagel was part of a 2023 study evaluating a large group of people at high risk of hereditary early-onset Alzheimer’s in Colombia that revealed physiological changes that are normally associated with the response to viral infection7. “We showed that familial Alzheimer’s patients actually had signatures of viral processes and infection in the olfactory bulb”, and more inflammation in the bundles of nerve fibres that run to these smell centres in the brain, compared with healthy individuals, says Nagel. The study did not try to identify the viruses themselves.

In 2010, Tanzi and long-time collaborator Robert Moir demonstrated that amyloid-β exerts potent antimicrobial effects in vitro3. The production of amyloid- might be a defense mechanism against pathogens according to the suggestion. In 2018, Moir, who died in 2019, and Tanzi demonstrated that herpesvirus infection induces the release and aggregation of amyloid-β both in cultured human brain cells and in mice4. Tanzi says that the plaque forms as an extracellular trap for the microbe.

It’s less than ideal to measure the antivirals in the blood because they could be from the brain or other parts of the body. There is no easy method to detect the viruses in brain-tissue samples. There are a lot of issues surrounding the validity of the methods used for detecting viral particles in autopsy samples.

Tanzi supports the latter hypothesis. The peripheral immune system and monocytes get into the brain when you get a vaccine, he says, and that helps to clear amyloid.

Some groups are trying to find evidence of a connection between shingles and dementia by looking at the incidence of the disease among people who have been vaccined. Early studies that sought to establish such a connection were vulnerable to biases that made their results impossible to interpret confidently. More health motivated people are more likely to get vaccinations, according to an epidemiological researcher at a California university.

He and others have made a case for the association of Alzheimer’s with a strong inflammatory response that causes amyloid- plaques and tangles in the brain. Gwenn Garden, a neurologist at the university of North Carolina at Chapel Hill, says that inflammatory mediators are present in the brain as it starts to accumulate amyloid. The inflammation is a result of early plaque formation, which creates a feedback loop to further accelerate amyloid- aggregation, but lifestyle and environmental factors might also create an inflammatory environment in the brain that favors Alzheimer’s.

When the varicella zoster virus is reactivated, it causes shingles and it takes a long time for the vaccine to kick in. It is characterized by extremely painful rash, but a growing number of clinicians and researchers believe it may also play a role in Alzheimer’s disease and other forms of dementia.

For a long time, this degenerative condition, in which memory loss and confusion build over a number of years, was viewed as an unstoppable force or even a natural consequence of ageing. We now know that neither is true. Although Alzheimer’s is not yet curable, a handful of treatments can slow its progression, and much work is being done to try to further turn the tide.

The first therapies for Alzheimer’s target the amyloid-, a substance that clumps together in the brain. The deposits are cleared to slow cognitive decline. The task now is to achieve stronger effects by building on anti-amyloid therapy or combining it with drugs that target other aspects of the disease.

Five years ago a breakthrough was the development of blood tests that could differentiate between Alzheimer’s and other forms of dementia. Although they look set to become crucial tools for physicians and researchers, there are apprehensions over their potential misuse.

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