Debating the Connection Between Herpesvirus Infection and Alzheimer's Disease

The role of persistent infection in the development of Alzheimer's disease is much debated these days, particularly now that the amyloid cascade hypothesis is under attack, following the continued failure of trials for therapies that clear amyloid-β. The biggest challenge in understanding Alzheimer's disease is the question of why only some people develop the condition, even given very similar lifestyle choices relating to weight, exercise, and other well-known influences on health. If the burden of persistent infection is an important contributing factor, it would very conveniently explain this otherwise puzzling outcome.

Herpesviruses and other persistent pathogens are hypothesized to contribute to the development of Alzheimer's via (a) greater chronic inflammation, and (b) greater generation of amyloid-β in its role as a part of the innate immune system response. The mechanisms make sense, but the data for herpesviruses in particular is contradictory, indicating that while herpesvirus infection may contribute to Alzheimer's disease, it likely isn't the major cause. Perhaps other persistent infections are also important. Or perhaps Alzheimer's is in fact a collection of distinct conditions with quite different roots that converge on the same situation of amyloid-β and inflammation in the brain.

New Data Questions Herpes-Alzheimer's Connection

The virus-Alzheimer's tug of war continues. New data across several studies weaken the proposed, and much-debated, association; its proponents are holding fast. A new epidemiology study reports a weak link between herpes and dementia. Researchers combed through four European population-wide healthcare databases and describe equivocal data. In Denmark and Wales, short-term antiviral drug use came with slightly fewer future dementia cases. Alas, in Germany and Scotland, this association did not hold. The opposite was also true; infected people who were not prescribed an antiviral had a slightly higher risk of dementia - but only in the German cohort. "The results are not very encouraging. Some of these associations held no matter what type of dementia or virus was considered. Because neither dementia subtype nor herpes subtype modified the association, the small but significant decrease in dementia incidence with antiherpetic administration may reflect confounding and misclassification."

Twenty-five years ago, researchers linked herpes simplex virus type 1 (HSV-1) infection with an increased risk of Alzheimer's disease (AD). She later spotted the virus hiding in amyloid plaques in brain tissue, and postulated that it may trigger the deposits. Since then, other connections have emerged. Scientists linked viral DNA in the brain to expression changes of genes involved in amyloid metabolism; others proposed that amyloid acts as an antimicrobial peptide.

Still, compelling evidence that viruses, particularly herpesviruses, cause AD remains elusive, although some researchers believe that the teeny irritants could speed disease along. The debate has taken on a new sense of urgency since reports that COVID-19 causes long-term neurological symptoms in a fraction of people who contract the disease. Scientists are just beginning to study this aspect of the infection. "Heterogeneous results are not terribly surprising given the complex nature of AD etiology and pathogenesis, which, so far, does not exclude an infectious component."

Comments

I am starting to think that the various persistent fungal, bacterial, parasitic and viral infections found in AD are just an indicator of poor immune function. Lifetime accumulation of their of unique microbial and viral burden coupled with their genetics and lifestyle choices determines their particular ailments and rate of decline. At different times I blamed one particular bug or another but now think it is "all" bugs.

Even in the so-called "healthy" and the young, the pathogens find and use exploits to get in. Otherwise, how would healthy children get sick?

Thymus rejuvenation will prove to be useful and add years of healthy life.

Posted by: Lee at February 4th, 2021 4:57 AM

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