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A newly published study has revealed a significant link between the gene most strongly associated with Alzheimer’s disease – APOE4 – and an increased risk of seizures. Researchers at the University of Illinois Urbana-Champaign have not only identified this connection but as well pinpointed a potential therapeutic pathway involving a common hypertension medication that appears to mitigate seizure activity. This discovery offers a new avenue for understanding and potentially managing neurological symptoms experienced by individuals at risk for or living with Alzheimer’s disease.

The research, published recently, sheds light on the complex interplay between genetic predisposition, brain hyperactivity, and the progression of Alzheimer’s. Approximately 10-22% of Alzheimer’s patients experience unprovoked seizures, while a much larger percentage – up to 50% – exhibit subclinical epileptic activity, characterized by hyperactivity in the brain. Understanding the root causes of this neurological phenomenon is crucial, as seizures themselves can accelerate cognitive decline and worsen dementia symptoms. The study aims to address the question of when and why this brain hyperactivity occurs, and whether it can be effectively intervened upon.

APOE4 Gene Disrupts Brain Cell Function

The investigation focused on the APOE4 gene, which is known to increase the risk of developing Alzheimer’s disease twelvefold compared to the more common APOE3 gene. Researchers discovered that the APOE4 gene impacts neuronal function by decreasing the levels of ion pumps and energy-producing enzymes within brain cells. This disruption leads to a reduction in the brain’s ability to maintain stable electrical activity, increasing the likelihood of seizures. The study specifically examined mice genetically modified to carry the human APOE4 gene to observe these effects.

“We already know that seizures increase dementia risk and accelerate its progression,” explained study leader Hee Jung Chung, a professor of molecular and integrative physiology at the University of Illinois Urbana-Champaign. “What we wanted to know in this study was when and why hyperactivity of the brain occurs in Alzheimer’s disease patients. Can we stop it? And if so, does that mitigate dementia risk and disease progression?”

Hypertension Medication Shows Promise in Reducing Seizures

Importantly, the researchers found that administering a medication commonly used to treat hypertension stimulated the energy-making pathway in the brains of the mice and significantly reduced seizure activity. This suggests that targeting the energy metabolism within neurons could be a viable therapeutic strategy for managing seizures in individuals carrying the APOE4 gene. The specific hypertension drug was not named in the available reports.

The timing of increased seizure activity was also identified. The mice began experiencing more frequent seizures and increased mortality related to seizures between 5.5 and 7 months of age, which researchers correlate to roughly equivalent to a human in their 30s. Younger mice, aged 2-3 months, showed no noticeable effects. This finding is significant because most studies examining Alzheimer’s-related brain activity focus on older populations, potentially missing crucial early-stage developments.

Alzheimer’s and Epilepsy: A Bidirectional Relationship

This research builds upon a growing body of evidence demonstrating a complex relationship between Alzheimer’s disease and epilepsy. A study published in Alzheimer’s Disease and Dementia highlights that individuals with epilepsy have a higher risk of developing dementia compared to the general population. Observational studies suggest a bidirectional link, meaning that Alzheimer’s can increase the risk of epilepsy, and vice versa.

Further research is underway to explore the precise mechanisms underlying this connection and to determine the optimal timing and dosage of potential therapeutic interventions. A separate study, published in Science Translational Medicine, identified a common anti-seizure drug that can prevent the formation of Alzheimer’s plaques, adding another layer to the potential for pharmacological intervention. Northwestern University scientists pinpointed when and where toxic proteins accumulate in the brains of Alzheimer’s patients, and found the drug could stop the accumulation process before it begins.

The findings from the University of Illinois study, coupled with ongoing research, underscore the importance of considering neurological symptoms, such as seizures, as potential indicators of early Alzheimer’s disease risk and as targets for therapeutic intervention. Further investigation is needed to translate these findings into effective treatments for humans, but the identification of a targetable pathway represents a significant step forward in the fight against this devastating disease.

As research continues to unravel the complexities of Alzheimer’s disease, a more holistic approach to diagnosis and treatment is emerging. The interplay between genetic factors, neurological symptoms, and metabolic processes is becoming increasingly clear, paving the way for more personalized and effective interventions. The next phase of research will likely focus on clinical trials to assess the efficacy of hypertension medications and anti-seizure drugs in preventing or slowing the progression of Alzheimer’s disease in humans.

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Disclaimer: This article is for informational purposes only and should not be considered medical advice. Please consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.