In recent years, viral infections have repeatedly been linked to the later occurrence of neurological and neurodegenerative diseases. For example, Epstein-Barr virus (EBV) is increasingly found in patients with multiple sclerosis. However, in addition to the effects of covid infection on the brain discussed earlier in this blog, bacterial inflammation also appears to be a possible cause of neurodegeneration. The large amounts of data now available in the context of biobanks allow for more rapid and unbiased detection of such associations.
A recent study published in the journal Neuron found a total of 22 significant and consistent associations between infection and the risk of developing neurodegenerative disease up to 15 years later in longitudinal data from a Finnish (FinnGen) and an English (UK) biobank. Among these, influenza (with or without pneumonia) was the endpoint most commonly associated with neurodegeneration in more than 300,000 Finnish and 500,000 English subjects.
Five of six diseases studied (Alzheimer's disease, amyotrophic lateral sclerosis, generalized dementia, vascular dementia, Parkinson's disease, and multiple sclerosis) were shown to correlate with viral infection. In addition to influenza, viral encephalitis, varicella-zoster, and an intestinal infection appear to have increased ability to trigger degenerative brain disease. Mechanistically, it seems most likely that via a strong stimulation of the general immune system, microglia cells in the brain are also activated. These cells can damage neurons if they are active for weeks and months.
Therapeutically relevant, vaccines are available for influenza, shingles and some pneumonias. Although they do not prevent all cases of illness, vaccines are known to dramatically reduce hospitalizations. This suggests that vaccination also reduces the risk of developing neurodegenerative disease. In fact, vaccinations against influenza and pneumonia were recently found to reduce the risk of Alzheimer's and Parkinson's disease. In addition to vaccination, the use of antivirals may also reduce the risk of dementia, for example, after infection with herpes simplex or varicella zoster viruses. Accordingly, although developing therapies that completely remove viruses from the body is a major challenge, stopping viral replication could further reduce risk factors for neurodegenerative diseases.
Reference:
Levine KS, Leonard HL, Blauwendraat C, Iwaki H, Johnson N, Bandres-Ciga S, Ferrucci L, Faghri F, Singleton AB, Nalls MA (2023) Virus exposure and neurodegenerative disease risk across national biobanks. Neuron 111:1086
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