Previously, sequencing mRNA in tissue samples was difficult because the molecules degrade very quickly. However, new technology specifically addresses that issue by measuring small subsections of mRNA at a time instead of trying to reconstruct the whole mRNA sequence at once.
We leveraged this technology to sequence the mRNA of olfactory bulb and olfactory tract samples from six people with familial Alzheimer’s, an inherited form of the disease, and six people without Alzheimer’s. We focused on familial Alzheimer’s because there is less variability in disease than in the sporadic, or nonfamilial, form of the disease, which can result from a number of different individual and environmental factors.
In the familial Alzheimer’s samples, we found altered gene expression indicating signs of a past viral infection in the olfactory bulb, as well as inflammatory immune responses in the olfactory tract. We also found higher levels of proteins involved in demyelination in the olfactory tract of familial Alzheimer’s samples than in the controls. Myelin is a protective fatty layer around nerves that allows electrical impulses to move quickly and smoothly from one area of the brain to another. Damage to myelin stalls signal transduction, resulting in impaired neural communication and, by extension, neurodegeneration.
Based on these findings, we hypothesize that viral infections, and the resulting inflammation and demyelination within the olfactory system, may disrupt the function of the hippocampus by impairing communication from the olfactory bulb. This scenario could contribute to the accelerated neurodegeneration seen in Alzheimer’s disease.
Epidemiological data supports the role of viral infections in the development of Alzheimer’s disease. For example, the varicella zoster virus is linked to a nearly threefold risk of developing dementia within five years of infection for patients with a shingles rash on their face. A recent report also found a nearly 70% increased risk of getting diagnosed with Alzheimer’s within a year of a COVID-19 diagnosis for people over 65.
These studies suggest that vaccination may be a potential measure to prevent dementia. For example, vaccination against the seasonal flu virus and herpes zoster is associated with an up to 29% and 30% reduced risk of developing dementia, respectively.
Further research investigating how viral infections can trigger neurodegeneration could aid in the development of antiviral drugs and vaccines against the viruses implicated in Alzheimer’s disease.
This article is republished from The Conversation, an independent nonprofit news site dedicated to sharing ideas from academic experts. It was written by: Andrew Bubak, University of Colorado Anschutz Medical Campus; Diego Restrepo, University of Colorado Anschutz Medical Campus, and Maria Nagel, University of Colorado Anschutz Medical Campus. The Conversation is trustworthy news from experts, from an independent nonprofit. Try our free newsletters.
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Andrew Bubak receives funding from the National Institute on Aging.
Diego Restrepo receives funding from the National Institute of Health and the National Science Foundation
Maria Nagel receives funding from the National Institutes of Health.