1 in 9 Americans over the age of 65 Alzheimer’s disease In 2022, countless people were indirectly affected as caregivers, healthcare providers and taxpayers. There is currently no cure. Available treatments mainly focus on prevention by encouraging protective factors such as exercise and a healthy diet. aggravating factorsuch as diabetes and high blood pressure.
One of these exacerbating factors is viral infection. Researchers have identified specific viruses such as: herpes simplex virus type 1 (HSV-1 that causes cold sores), varicella zoster virus (VZV, which causes chickenpox and shingles) and SARS-CoV-2 (causing COVID-19) may increase the risk of Alzheimer’s disease and dementia after infection.
Unraveling how and when these viruses contribute to disease could help scientists develop new treatments. prevent dementiaHowever, researchers Consistently undetectable The virus is suspected 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 believe the virushit and run” Manners; they set off a cascade of events that lead to dementia, but have already begun. In other words, by the time researchers analyze a patient’s brain, all detectable viral components are gone, making it difficult to establish causality.
we neurovirologist, neurologist When neuroscientist The team is interested in the role of viruses in neurodegenerative diseases.in us recently published research, using new technology to search for these viral tire tracks in Alzheimer’s patients. By focusing on the most vulnerable entry point into the brain, the nose, we have discovered a genetic network that provides evidence for a strong viral response.
Commitment to the olfactory system
Many of the viruses involved in dementia are herpes virus and the Virus that causes COVID-19enters the nose and interacts with the olfactory system.
of olfactory system We are constantly exposed to odors, contaminants and pathogens. Particles inhaled through the nostrils bind to specific olfactory receptor cells in the tissue lining the nasal passages. These receptors send messages to other cells called the olfactory bulb. The olfactory bulb acts like a relay station that transmits these messages to long nerves in the olfactory tract. These messages are forwarded to the hippocampus, the region of the brain responsible for learning and memory.
The hippocampus plays an important role in assigning contextual information to odors, such as the dangers of propane odors and the comfort of odors. scent of lavenderThis area of the brain is also dramatically damaged in Alzheimer’s disease, causing devastating learning and memory deficits. loss of smell It is an early symptom of the disease.
The mechanism by which the sense of smell is lost in Alzheimer’s disease is largely unknown. Like a muscle that atrophies when not used, sensory deprivation It is thought to lead to atrophy of brain regions that specialize in interpreting sensory information. Strong sensory input to these areas is important for maintaining general brain health.
Olfactory inflammation and Alzheimer’s disease
We hypothesize that lifelong viral infections contribute to AD as well as being a potential drug target for AD. To test this idea, Investigated using state-of-the-art technology mRNA and protein networks of the olfactory system in patients with Alzheimer’s disease.
used by the body mRNA, which is transcribed from DNA and translates genetic material into proteins. The body uses specific mRNA sequences to generate networks of proteins used to fight certain viruses.Sometimes the body keeps moving activate these pathways Even after the virus is cleared, it leads to chronic inflammation and tissue damage. By identifying which mRNA sequences and protein networks are present, we can make some inferences as to whether the body is responding to a viral pathogen at any given time.
Previously, sequencing mRNA in tissue samples was difficult because the molecule degrades so rapidly. but, New technology specifically address this issue by measuring small subsections of mRNA at once, rather than trying to reconstruct the entire mRNA sequence at once.
Using this technology, we sequenced mRNA from olfactory bulb and tract samples from six individuals with the genetic disorder familial Alzheimer’s disease and six individuals without Alzheimer’s disease. We focused on familial Alzheimer’s disease because the disease is less variable than sporadic or non-familial diseases and can be attributed to many different individual and environmental factors.
In familial Alzheimer’s disease samples, we found alterations in gene expression indicative of a previous viral infection in the olfactory bulb and an inflammatory immune response in the olfactory tract. We also found proteins involved in demyelination at higher levels in the olfactory pathways of familial Alzheimer’s disease samples than in controls. Myelin It is the protective fatty layer around nerves that allows electrical impulses to travel quickly and smoothly from one area of the brain to another. Damage to myelin shuts down signaling, leading to impaired neurotransmission and, in turn, neurodegeneration.
Based on these findings, we hypothesize that viral infection, and the resulting inflammation and demyelination within the olfactory system, may disrupt hippocampal function by impairing communication from the olfactory bulb. This scenario may contribute to the accelerated neurodegeneration seen in Alzheimer’s disease.
Impact on patient health
Epidemiological data support a role for viral infections in the development of Alzheimer’s disease. for example, varicella zoster virus Patients with a shingles rash on the face almost triple the risk of developing dementia within five years of infection. Nearly 70% more risk Percentage of people aged 65 and older who are diagnosed with Alzheimer’s disease within one year of being diagnosed with COVID-19.
These studies suggest that vaccination may be a potential means of preventing dementia.For example, vaccination seasonal influenza virus When Herpes zoster Reduces risk of developing dementia by up to 29% and 30% respectively.
Further research investigating how viral infections cause neurodegeneration may help develop antiviral drugs and vaccines against the viruses implicated in Alzheimer’s disease.
report written by Andrew BabakAssistant Professor of Neurology. Diego Restrepo, Professor of Cellular and Developmental Biology.When Maria NagelProfessor of Neurology and Ophthalmology, All University of Colorado Anschutz Medical Campus. This article is reprinted from conversation Under Creative Commons License.read Original work.
