Vaccination to prevent dementia? New research suggests one way viral infections can accelerate neurodegeneration

One in nine Americans age 65 and older has it Alzheimer’s disease In 2022, and countless others have been indirectly affected such as caregivers, healthcare providers, and taxpayers. There is currently no cure – available treatments focus primarily on prevention by encouraging and reducing protective factors, such as exercise and a healthy diet aggravating factorssuch as diabetes and high blood pressure.

One such aggravating factor is viral infections. Researchers have identified that some viruses such as Herpes simplex virus type 1 (HSV-1, which causes cold sores), Varicella zoster virus (VZV, which causes chickenpox and shingles) f SARS-CoV-2 (which causes COVID-19) can lead to an increased risk of Alzheimer’s disease and dementia after infection.

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Figuring out how and when these viruses contribute to disease could help scientists develop new treatments to prevent dementia. However, researchers have been Unable to detect continuously It is suspected that viruses were present in the brains of people who died of Alzheimer’s disease. Because the Alzheimer’s disease process can begin decades before symptoms appear, some researchers have suggested that viruses act early in the disease.Hit-and-runmethod; they trigger a chain of events that leads to dementia but has already begun. In other words, by the time researchers analyze patients’ brains, any detectable viral components are gone and causation is hard to pin down.

we NeurovirologistAnd neurologist And nerves A team interested in the role viruses play in neurodegenerative diseases. in our area Recently published researchIn this study, we use a new technique to search for tire pathways of these viruses in Alzheimer’s patients. By focusing on the most vulnerable entry point into the brain, the nose, we uncovered a genetic network that provides evidence for a robust viral response.

Focus on the olfactory system

Several viruses implicated in dementia include herpes viruses; and the The virus that causes COVID-19It enters the nose and interacts with the olfactory system.

the Olfactory system It is constantly exposed to odors, pollutants, and pathogens. Molecules inhaled through the nostrils bind to specific olfactory receptor cells in the tissues lining the nasal cavity. These receptors send messages to other cells in the so-called olfactory bulb, which acts as a relay station transmitting these messages to the long nerves of the olfactory tract. These messages are then transmitted to the region of the brain responsible for learning and memory, the hippocampus.

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The hippocampus plays a critical role in assigning contextual information to odors, such as danger from the unpleasant odor of propane or relief from odors. Lavender scent. This area of ​​the brain is also significantly damaged in Alzheimer’s disease, causing devastating learning and memory deficits. For up to 85% to 90% of Alzheimer’s patients, loss of sense of smell It is an early sign of disease.

The mechanism that leads to the loss of smell in Alzheimer’s disease is relatively unknown. Like muscles that atrophy from lack of use, sensory deprivation It is thought to atrophy areas of the brain that specialize in interpreting sensory information. Strong sensory input to these regions is critical to maintaining overall brain health.

Olfactory inflammation and Alzheimer’s disease

We hypothesize that viral infection throughout life are contributory factors and potential drug targets in Alzheimer’s disease. To test this idea, We used the latest modern technology for investigation mRNA and protein networks in the olfactory system of Alzheimer’s patients.

The body is used mRNA, which are copied from DNA, to translate the genetic material into proteins. The body uses certain messenger RNA sequences to produce a network of proteins that are used to fight off certain viruses. In some cases, the body persists activate these pathways Even after the virus is removed, it leads to chronic inflammation and tissue damage. Identification of the mRNA sequences and protein networks present can allow us to infer, to some extent, whether the body is or has been responding to a viral pathogen at some point.

Previously, sequencing of mRNA sequences in tissue samples has been difficult because the molecules degrade so quickly. But, new technology It specifically addresses this problem by measuring small subsections of mRNA at a time rather than trying to reconstruct the entire mRNA sequence at once.

We took advantage of this technology to sequence mRNA of olfactory bulb and olfactory tract samples from six people with familial Alzheimer’s disease, an inherited form of the disease, and six people without Alzheimer’s disease. We focused on familial AD because there is less variability in the disease than in the sporadic or non-familial form of the disease, which can result from a number of different individual and environmental factors.

Micrograph of neurons in the olfactory bulb of a mouse
This image shows neurons in a small cross-section of the mouse olfactory bulb. (credit: Jeremy McIntyre/University of Florida School of Medicine via the National Institutes of HealthCC BY-NC)

In familial Alzheimer’s disease samples, we found altered gene expression suggestive of markers of previous 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 compared to the control group. myelin It 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 stops signal transmission, leading to impaired nerve communication and, in turn, neurodegeneration.

Based on these findings, we hypothesize that viral infections, and demyelinating inflammation within the olfactory system, may disrupt hippocampal function by impairing communication from the olfactory bulb. This scenario could contribute to the acceleration of neurodegeneration observed in Alzheimer’s disease.

Implications for the patient’s health

Epidemiological data support a role for viral infection in the development of Alzheimer’s disease. For example, file Varicella zoster virus It is associated with an almost 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 file Almost 70% increase in risk of a diagnosis of Alzheimer’s disease within a year of a diagnosis of COVID-19 for people over 65 years of age.

These studies suggest that vaccination may be a potential dementia prevention measure. For example, vaccination against seasonal influenza virus And herpes zoster; It is associated with a reduced risk of dementia by up to 29% and 30%, respectively.

Additional research looking at how viral infections cause neurodegeneration could inform the development of antiviral drugs and vaccines against viruses implicated in Alzheimer’s disease.

Report by Andrew BobakAssistant Research Professor of Neurology; Diego Restrepo, professor of cellular and developmental biology; And Maria NagelProfessor of Neurology and Ophthalmology, all from University of Colorado Anschutz Medical Campus. This article has been republished from Conversation Under Creative Commons Licence. Read the The original article.

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