Transplant Drug Shows Promise in Slowing Alzheimer’s in Seizure Patients

Protein imbalances, which heighten the excitability of brain cells, may elucidate the accelerated cognitive decline observed in individuals with Alzheimer’s disease (AD) who also suffer from seizures. These imbalances could manifest in the brains of individuals even before the onset of AD symptoms. This recent discovery, presented by a research team at the University of Pennsylvania’s Perelman School of Medicine, has been unveiled in the latest issue of Brain.

The team unveiled that rapamycin, an existing drug initially designed as an immunosuppressant for organ transplant patients to dampen neuronal signaling, effectively regulated the hyper-excited neurons in mouse models exhibiting AD and seizures. Moreover, it managed to preserve cognitive functions such as memory and learning capabilities.

Previous studies have illustrated similar neural patterns in individuals with AD who experience epilepsy. Furthermore, many AD patients have encountered at least one seizure, with prior research indicating that such seizures hasten disease progression and exacerbate cognitive impairment. Nevertheless, researchers have hitherto failed to pinpoint the underlying correlations between AD and seizures.

“Conventional wisdom once held that seizures were a regrettable side effect of the neurodegeneration inherent in Alzheimer’s disease. However, we now perceive seizures as catalysts that expedite the disease’s progression,” remarked Frances E. Jensen, MD, co-senior author of the study and chair of Penn’s Department of Neurology. “Now that we have unraveled the mechanisms underlying neuronal hyper-excitability and its acceleration of AD, we can delve into therapies like rapamycin, capable of rectifying the imbalance and decelerating AD progression.”

In a healthy brain, two neurotransmitters collaborate to regulate neuronal communication. Glutamate facilitates excitatory signaling between cells, dictating when neurons should transmit messages. Meanwhile, GABA oversees inhibitory signaling, reducing the likelihood of cell firing and indicating when signaling should cease.

This study analyzed post-mortem tissue from AD patients who had experienced seizures, discovering dysregulation in certain forms of these neurotransmitters. Neurons in these individuals exhibited heightened excitability and diminished inhibition, resulting in excessive neuronal signaling, termed as a “hyperactive brain” by researchers. Medical records of these patients confirmed inferior cognitive evaluation scores compared to AD patients without seizures.

To pinpoint the onset of this dysregulation in AD, researchers monitored brain activity in AD mouse models with seizures. They observed heightened excitability and decreased inhibition in neurons even at preliminary disease stages, preceding cognitive symptom manifestation.

“By the time many individuals are diagnosed with Alzheimer’s disease and commence treatment, their disease is advanced, and substantial cognitive function has already deteriorated,” explained Aaron Barbour, PhD, co-senior author and postdoctoral researcher in the Department of Neurology. “Our research marks an exciting stride toward intervening with treatment before symptom onset to mitigate the disease’s devastating impact.”

Source Link