Viruses have been considered a controversial risk factor for Alzheimer’s for decades. It is a contentious hypothesis regarding the disease, frequently brushed aside by specialists as a dubious offshoot of accepted knowledge.

However, research continued to establish whether they have a role in the development of Alzheimer’s. Two recent studies have lent some support to this controversial idea.

Involvement of Herpes Virus in Alzheimer’s

In 2018, a team, including eminent Alzheimer’s researchers who had previously questioned this idea, conducted a study that supported the claim of the involvement of viruses in Alzheimer’s. The study, published in the journal Neuron, provides compelling evidence that viruses, notably two forms of herpes (HHV-6A and HHV-7) that most individuals contract as babies and which subsequently go latent for years, may have a role in Alzheimer’s disease.

According to the study, viruses interact with genes associated with Alzheimer’s and may influence how the disease manifests itself and advances. The researchers discovered much more viral genetic material in Alzheimer’s-affected brains than in healthy ones. In addition, viral RNA levels in Alzheimer’s brains were higher than in the brains of healthy individuals for both HHV-6A and HHV-7, and they correlated with the severity of clinical symptoms. HHV-6A is a late-life virus that typically causes no symptoms. More than 80% of newborns have HHV-7 infection, which frequently results in a rash.

They discovered numerous interactions, indicating that the viruses might turn on and off genes relevant to Alzheimer’s. The researchers bred mice lacking one molecule that herpes appeared to deplete to determine if those interactions mattered. Indeed, more amyloid plaques appeared in the mice.

The authors clearly stated that they had not discovered that these viruses directly cause Alzheimer’s. However, their research, coupled with another soon-to-be-published study, reveals that viruses could trigger an immunological response that might accelerate the accumulation of amyloid, a protein in human brains that aggregates into the unmistakable plaques of Alzheimer’s.

The Role of Herpes and Varicella Zoster Viruses

Another recent study published in the Journal of Alzheimer’s disease has further strengthened the notion that viruses may play a role in Alzheimer’s development. The study showed how the Herpes Simplex Virus (HSV-1) could interact with the related varicella zoster virus (VZV), which causes chickenpox and shingles, to trigger the early stages of dementia. In the early 1990s, Ruth Itzhaki (one of the study’s researchers) initially demonstrated that HSV-1 is dormant in the brains of many older individuals.

Researchers discovered that VZV might activate HSV-1 in the brain, causing an accumulation of tau and amyloid proteins and a loss of neuronal function—markers of Alzheimer’s disease—in a three-dimensional neural tissue culture model of the brain developed at Tufts. VZV didn’t do anything on its own.

One of the authors, Dana Cairns, stated that although they found a connection between VZV and HSV-1 activation, other inflammatory brain events (like head trauma) may potentially awaken HSV-1 and cause Alzheimer’s.

Researchers are trying to gather more concrete evidence concerning the involvement of HSV-1 in Alzheimer’s via clinical trials at Columbia University and the New York State Psychiatric Institute. They have given the participants in the early stages of the illness having an HSV-1 infection either valacyclovir, an antiviral medication, or a placebo. The trial is to be completed in December 2023.

Impact of Covid-19 on the Alzheimer’s Research

As more evidence mounts that Sars-Cov-2, the virus that causes Covid, can harm the brain in some people, interest in the connections between viruses and dementia has also grown due to the Covid-19 pandemic.

Researchers at Oxford University extensively studied and reported the chronic neurological and psychological effects of Sars-Cov-2. They examined the electronic health data of 1.25 million Covid patients and a control group of patients with comparable respiratory illnesses. In the following two years, 4.5% of Covid patients 65 or older acquired dementia, compared to 3.3% of the control group.

However, the research had limitations since the first case of Covid was recorded less than three years ago, and the researchers did not have enough time to follow up to understand the implications of Covid for people who may develop dementia in the future. The initial neural triggers that cause Alzheimer’s symptoms can take longer to manifest.

Itzhaki believes that by reactivating latent HSV-1 in the brain, Sars-Cov-2, like VZV, raises the risk of Alzheimer’s. ApoE4 gene carriers seem to be especially susceptible. To investigate it, Neurologists from 25 countries have set up a worldwide collaboration: The Alzheimer’s Association Consortium on Chronic Neuropsychiatric Sequelae of Sars-Cov-2 Infection.

Sources

1. Readhead, B., Haure-Mirande, J.V., Funk, C.C., Richards, M.A., Shannon, P., Haroutunian, V., Sano, M., Liang, W.S., Beckmann, N.D., Price, N.D. and Reiman, E.M., 2018. Multiscale analysis of independent Alzheimer’s cohorts finds disruption of molecular, genetic, and clinical networks by human herpesvirus. Neuron, 99(1), pp.64-82. https://www.cell.com/neuron/fulltext/S0896-6273(18)30421-5?_.
2. Cairns, D.M., Itzhaki, R.F. and Kaplan, D.L., 2022. Potential Involvement of Varicella zoster virus in Alzheimer’s disease via reactivation of quiescent Herpes simplex virus type 1. Journal of Alzheimer’s Disease, (Preprint), pp.1-12. https://content.iospress.com/articles/journal-of-alzheimers-disease/jad220287.
3. Taquet, M., Sillett, R., Zhu, L., Mendel, J., Camplisson, I., Dercon, Q. and Harrison, P.J., 2022. Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1 284 437 patients. The Lancet Psychiatry, 9(10), pp.815-827. https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(22)00260-7/fulltext.
4. https://www.alz.org/research/for_researchers/partnerships/sars-cov2-global-brain-study