How can the pharmaceutical Leqembi slow the progression of Alzheimer’s disease?

Teachable moment in classrooms:

1. nervous system chapter – functions of neurons
2. nervous system chapter – function of synapses in neuronal communication
3. immune system chapter – role of antibodies to speed up phagocytosis
4. blood chapter – function of neutrophils, monocytes and macrophages

The news item:  Recently the following report appeared online:

First Alzheimer’s drug to slow disease, Leqembi, gets full FDA approval

Leqembi is not a cure, but it is the first drug shown to slow the progression of Alzheimer’s disease. It first received an accelerated approval from the FDA earlier this year.

The article states that Leqembi slows the progression of Alzheimer’s disease in early stage Alzheimer’s patients, because Leqembi can remove the disease-causing plaques from the brain, and prevent their formation. The article also states that the plaques prevent neurons from talking to each other.

So, Why Do I Care??  Alzheimer’s disease (dementia) affects almost 7 million people in the USA. The memory loss at first  reduces the quality of life, and then makes the patients dependent on daily nursing care. All the while the patients no longer recognize family members, or items in their environment, making it difficult on the families. Because there is no effective treatment or prevention for it, pharmaceuticals even with moderate effectiveness can have positive impact on both the patients and the families.

Plain English, Please!!!

First, let’s talk about what Alzheimer’s disease is. Recalling memories is a function assigned to groups of neurons, sometime called neuronal circuits. Each circuit may have thousands or millions of neurons, and the communication between the members keep the circuit functioning. Each time you remember something, neurons of a memory circuit are activated. Think about the “wave” you see in sporting events where the spectators stand up and raise their arms and then sit down forming a moving “wave. Each spectator is a neuron, and their collective action produces a “wave”, the recalling of a memory. In Alzheimer’s disease the neurons of the memory circuits malfunction, and when those neurons try to act in a coordinated fashion, their activity, their “wave”, their recall of memory becomes weaker leading to loss of memory. A few years into the disease large number of neurons may malfunction and die and complete the loss of memory may happen.

Second, let’s talk about why neurons are thought to die in Alzheimer’s disease. The most widely accepted theory is that the buildup of clumps of amyloid peptide, also called senile plaques, outside the neurons cause their death.  The clumps disrupt the functioning of the synapses, which then causes poor communication between the neurons, and the malfunctioning of the memory circuits.  The senile plaques also cause local inflammation, and that causes the death of neurons. Imagine if garbage would not be picked up from our households but remain at the street for months. Such accumulation of waste products has harmful consequences for neurons and people alike.

Third, let’s talk about how can Leqembi improve conditions of Alzheimer’s patients. It makes intuitive sense that if we could prevent the formation of the plaques, and remove the existing ones, then we could slow the start and the progress of the memory loss. Antibodies made by our own immune system stick to bacteria and viruses, and mark them for destruction by neutrophils, monocytes and macrophages.  Leqembi is an artificial antibody that, after infusion into the blood stream, sticks to the plaques in the brain, so neutrophils, monocytes and macrophages then phagocytose and digest the plaques. 75% of treated early Alzheimer’s patients became amyloid free, and that slowed by 27-47% the progression of their memory loss.