Scientists at Weill Cornell Medicine have found a new potential approach to treating Alzheimer’s disease and frontotemporal dementia, two of the most common forms of dementia in older people.
The researchers have discovered that targeting a specific part of the body’s natural defense mechanism against pathogens, which can trigger cognitive decline, may offer a new therapeutic approach.
The study focused on the innate immune system, which is the body’s first line of defense against pathogens.
The researchers found that inhibiting an enzyme called cyclic GMP-AMP synthase (cGAS) helped neurons become more resistant to the build-up of the protein tau into bundles known as fibrils, a hallmark of Alzheimer’s and some forms of frontotemporal dementia.
The study’s senior author, Dr. Li Gan, said, “We are interested in this antiviral pathway because of its importance in modulating innate immunity, which emerges as a major driver in neurodegenerative dementia.”
The researchers found that when immune cells in the nervous system, called microglia, were exposed to abnormal tau, the mitochondria or organelles that produce a cell’s energy leaked DNA into the cell fluid.
The immune system recognized this mitochondrial DNA leakage as a viral invasion and activated the enzyme cGAS.
This enzyme then triggered the sustained release of the immune system protein type I interferon (IFN-I).
The sustained IFN-I signaling from microglia decreased the activity of a protein called myocyte enhancer factor 2c (MEF2C), which is a molecular switch that provides neurons with the blueprint to function normally and resist cognitive decline.
By inhibiting the antiviral response both genetically and pharmacologically, the researchers were able to turn the switch on to instruct normal neuronal function, even in brains loaded with tau bundles.
The researchers conducted laboratory studies in an Alzheimer’s disease mouse model and used single-nuclei RNA sequencing to study gene expression in individual cells genome-wide.
They found that removing the cGAS gene in the mice dampened the immune response of microglia and IFN-I.
This preserved the function of synapses and protected against cognitive decline function regardless of the accumulation of abnormal tau protein.
The researchers also discovered that a small molecule cGAS inhibitor could restore MEF2C activity and improve memory function in mice with abnormal tau proteins.
The inhibitor also modulated the antiviral pathway in human microglia derived from induced pluripotent stem cells.
These findings offer hope for the development of new treatments for Alzheimer’s and frontotemporal dementia that target the body’s natural defense mechanism.
Further studies are needed to explore the efficacy of cGAS inhibitors and their potential as a therapeutic approach to these diseases.
How to prevent frontotemporal dementia
Frontotemporal dementia (FTD) is a progressive brain disorder that affects a person’s behavior, language, and decision-making abilities.
Unfortunately, there is currently no cure for FTD, and treatments mainly focus on managing the symptoms of the disease.
However, there are some lifestyle changes that may help prevent or delay the onset of FTD. Here are a few tips:
Exercise regularly: Regular exercise can improve overall health and reduce the risk of developing various neurological disorders, including FTD. Exercise increases blood flow to the brain, which helps keep it healthy and functioning correctly.
Maintain a healthy diet: Eating a healthy and balanced diet can help reduce the risk of developing FTD. A diet rich in fruits, vegetables, whole grains, and lean protein sources can help reduce the risk of developing neurological disorders.
Stay mentally active: Keeping the brain active can help prevent or delay the onset of FTD. Activities such as reading, doing puzzles, learning new skills, and socializing can help keep the brain healthy and functioning correctly.
Manage stress: Chronic stress can damage the brain and increase the risk of developing neurological disorders such as FTD. Managing stress through relaxation techniques such as yoga, meditation, or deep breathing exercises can help keep the brain healthy.
Get enough sleep: Lack of sleep can have a significant impact on brain function and increase the risk of developing neurological disorders. Getting enough sleep each night is essential for overall brain health.
If you care about brain health, please read studies about vitamin D deficiency linked to Alzheimer’s and vascular dementia, and higher magnesium intake could help benefit brain health.
For more information about brain health, please see recent studies about antioxidants that could help reduce dementia risk, and coconut oil could help improve cognitive function in Alzheimer’s.
The study was conducted by Joe C. Udeochu et al and published in Nature Neuroscience.
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