- In some people, viruses can trigger the amyloid plaque buildup and inflammation associated with Alzheimer’s disease (AD) in the brain.
- There is a growing body of evidence linking the activation of the common herpes virus to the onset of dementia and anti-herpes treatments to reduce the risk of dementia.
- Using 2D and 3D models of herpes-induced AD, scientists have found that certain herbal constituents reduce amyloid plaques with minimal toxic effects.
- Researchers have reported that compounds in green tea and resveratrol help reduce plaque formation and protect neuronal function..
Alzheimer’s disease (AD), the most common type of dementia, causes cognitive decline and memory loss. Experts have yet to understand exactly how this debilitating neurological disorder develops and progresses.
The impact of AD on the brain includes plaque buildup, increased brain immune cells, neuroinflammation, and altered neuronal signaling.
Mounting evidence suggests that herpes simplex virus (HSV-1) reactivation may be responsible for causing these features.
Tufts University researchers recently constructed 2D and 3D human brain tissue models of herpes-induced AD to test the neuroprotective potential of pharmaceutical and herbal compounds.
Research associate Dr. Dana Cairns, who led the investigation, said these findings “provided some of the first evidence for direct causation of HSV-1 in AD in human brain tissue.”
In his team’s analysis, compounds in green tea called catechins (GTCs) and resveratrol stood out for their “strong anti-plaque properties, functional neuroprotective benefits, and minimal neurotoxicity.”
The study appears in the journal Free radical biology and medicine.
Tufts’ team believed that their model’s “rapid and robust” simulation of Alzheimer’s disease symptoms could provide a platform to test for neuroprotective compounds.
They looked at 21 compounds, including FDA-approved non-AD drugs, dietary and herbal supplements, and nutraceuticals known to be anti-inflammatory, “anti-aging,” or pro-cognitive. These included caffeine, camphor, citicoline, GTC, insulin, metformin, resveratrol and zolmitriptan.
The pro-cognitive effect of green tea
Green tea consumption has demonstrated the potential to reduce cognitive dysfunction in observational studies.
GTCs from green tea leaves may target amyloid misfolding which is a common mechanism in AD, a 2021 study finds Biomolecules study.
Physician and author Dr. Michael Greger, who was not involved in this study, discussed the antiviral properties of green tea in an April 2021 podcast:
“Unlike antiviral drugs, green tea appears to help by boosting the immune system, improving the proliferation and activity of gamma delta T cells, a type of immune cell that acts as a ‘frontline defense against infection.’ .”
The doctor also claimed that GTC can help reduce oxidative damage, fight inflammation and encourage DNA repair.
Activation of resveratrol and sirtuin
Resveratrol is found in grapes, nuts and other foods. As a sirtuin 1 activator, this polyphenol is under clinical investigation for its therapeutic potential in AD.
Dr. Greger explained the role of sirtuins in a September 2022 podcast:
“Each of us has six billion miles of DNA. How does our body keep it from getting tangled? There are special proteins called histones, which act like coils, with DNA as the common thread. Enzymes called sirtuins wrap the DNA around the histone coils and in doing so silence any genes that were in that part of the DNA, hence their name SIRtuins, which stands for information regulatory silence. .
“[The l]Loss of sirtuin enzyme activity is closely associated with the buildup of plaques and tangles in the brain that are hallmarks of Alzheimer’s disease. Sirtuins appear to activate pathways that steer the brain away from plaque and protein tangles.
— Dr. Michael Greger
Dr. Cairns and his colleagues hypothesize that certain compounds may help reduce plaque formation and protect neural network function.
In an interview with Medical News Todayshe shared, “We were excited to find some of these compounds and supplements that showed some level of effectiveness because maybe they would indicate that patients or anyone who wants to lower their risk of Alzheimer’s in the future can easily access it.”
The team’s first review of nearly 100 herbal drugs and supplements highlighted citicoline, curcumin, GTC, metformin, and resveratrol for potential to dissolve amyloid plaque. Dr Cairns said DTM that GTC and resveratrol were “two ‘star players’ that emerged” above the other contenders.
These underwent further neuroprotection testing.
They genetically reprogrammed fibroblasts, a cell type involved in the formation of connective tissue, into neural stem cell progenitors. These neural stem cells were then seeded into a silk sponge, populating the sponge and creating a 2D or 3D culture.
Next, the researchers infected the cultures with HSV. Amyloid plaque deposits, increased brain immune cells, and neuroinflammation developed in three days with the 2D model and one week with the 3D model.
In the primary 2D experiment, treatment with GTCs “reduced plaque formation and cell viability” compared to those treated with the antiviral drug valacyclovir and untreated infected cells. In addition, the size and number of plaques decreased to those of uninfected cells.
GTC-treated 3D fabrics showed a similar effect.
Similarly, resveratrol “provided nearly complete plaque removal” in both 2D and 3D displays. This biochemical has also shown minimal toxicity.
Dr Cairns expressed concern that future studies may depend on entities that are not financially motivated, which can be difficult to find.
Potential funders looking for a return on their research investment have no financial incentive to explore herbal supplements, she said.
The current study leader acknowledged that his lab’s brain tissue models leave out important features such as blood flow and an intact immune system.
Dr. Cairns also cautioned that his findings offer no guarantee that consuming certain amounts of the compounds selected by the team will benefit everyone equally.
“Some of these nutraceuticals or other compounds are better absorbed in the presence of fats or […] the foods they contain […] Plus you don’t know what you’re getting [in commercial supplements]so it can also be tricky.
—Dr. Dana Cairns
However, Cairns believes his findings may “open the door for pharmaceutical companies to take advantage of some of these mechanisms that show their effectiveness. They could then take the active compounds and modify them in some way to make them more available to brain tissue.