Rapamycin: Potential to Slow Alzheimer's Disease in Seizure Patients

Seizures are experienced by around 22% of individuals diagnosed with Alzheimers disease (AD). The presence of seizures worsens the progression of AD pathology and cognitive impairments. This indicates that targeting seizures could potentially help in managing the advancement of AD (1^✔ ✔Trusted Source
Organ transplant drug may slow Alzheimer’s disease progression in individuals with seizures

Go to source). Researchers at the University of Pennsylvania’s Perelman School of Medicine have found in a study the link between Alzheimer’s disease (AD) and seizures. They have published the study details in the journal Brain.

Individuals suffering from AD and seizures show accelerated cognitive decline as compared to those without seizures. This could be attributed to protein imbalances that increase brain cell excitability. The imbalances could potentially exist in the brains of individuals prior to the manifestation of symptoms associated with AD.

The group discovered that rapamycin, a drug created as an immunosuppressant for patients undergoing organ transplants to suppress communication between neurons, effectively controlled hyperactive neurons in mouse models experiencing Alzheimer's disease and seizures. Furthermore, it helped maintain cognitive abilities such as memory retention and learning capacity.

Previous studies have demonstrated comparable brain activity among individuals with AD who suffer from epilepsy. Moreover, a significant number of AD patients have encountered at least one seizure, and previous research has indicated that these seizures accelerate the advancement of the disease and exacerbate cognitive decline, such as difficulties with memory or learning. Nevertheless, the underlying links between AD and seizures have yet to be determined by researchers (2^✔ ✔Trusted Source
Seizures exacerbate excitatory: inhibitory imbalance in Alzheimer’s disease and 5XFAD mice

Go to source).

The study’s co-senior author, Frances E. Jensen, MD, chair of Penn’s Department of Neurology said, “Experts used to believe that seizures were an unfortunate byproduct of the neurodegeneration that causes Alzheimer’s disease, but now we see that seizures are actually advancing the disease itself,”.

Jensen further added, “Now that we have identified the mechanisms that cause neurons to get over-excited and lead to seizures that accelerate AD, we can explore therapies, like rapamycin, that can reverse the imbalance, and slow AD progression.”

Advertisement

In a normal brain, two neurotransmitters collaborate to regulate communication between neurons. Glutamate facilitates excitatory signals between cells, instructing neurons when to transmit a message. On the other hand, GABA controls inhibitory signals that decrease the likelihood of firing, instructing the cell when to cease communication.

Researchers in this investigation analyzed post-mortem tissue from individuals with AD who had encountered at least one seizure, and found an imbalance in specific neurotransmitter forms. The neurons in these subjects displayed heightened excitability and reduced inhibition, leading to an excessive transmission of signals between neurons in the brain, a condition termed "hyperactive brain" by researchers. Furthermore, the medical records of these patients indicated poorer cognitive assessment results compared to AD patients without a history of seizures.

Advertisement

Researchers monitored the brain activity of mouse models with AD with seizures, to determine the stage at which this dysregulation gets triggered. They discovered heightened excitability and reduced inhibition in neurons, even during the early stages of the disease, prior to the manifestation of cognitive symptoms.

A postdoctoral researcher in the Department of Neurology, and co-senior author, Aaron Barbour, PhD, said, “By the time many individuals are diagnosed with Alzheimer’s disease and start receiving treatments, their disease is advanced, and they have lost significant cognitive function,”. Barbour further added, “Our research is an exciting step towards being able to intervene with a treatment before symptoms develop to slow the devastating effects of the disease.”

This research shows a link between AD and seizures, highlighting the potential for seizures to accelerate the progression of the disease. Insights into such approaches enables researchers to investigate treatments that could impede the advancement of AD.

References:

1. Organ transplant drug may slow Alzheimer’s disease progression in individuals with seizures - (https://penntoday.upenn.edu/news/organ-transplant-drug-may-slow-alzheimers-disease-progression-individuals-seizures)
2. Seizures exacerbate excitatory: inhibitory imbalance in Alzheimer's disease and 5XFAD mice - (https://pubmed.ncbi.nlm.nih.gov/38662500/)

Source-Eurekalert