Cell Biology and Alzheimer’s Disease Treatment Paths

Sociology and Psychology

Photo by: Coey Yeung

Our brain consists of billions of neurons that play a major role in our central nervous system.

These neurons are specialized cells that transmit information via electrical and chemical signals. When a neuron receives a signal from another neuron, it travels down the axon and releases neurotransmitter chemicals across the synapse. Scientists estimate that one neuron may have as many as 7,000 synaptic connections with neighboring neurons. However, Alzheimer’s disease disrupts this communication process where neurons are injured or die throughout the brain. These neurons control other vital processes such as brain metabolism and repair, and it is the dynamic metabolic changes occurring in neurons that result in the loss of brain function and cell death, where the brain ultimately stops retrieving memories.

One hundred years ago, Alois Alzheimer examined the brain of Auguste D, a woman that carried dementia that developed cognitive deficiency in her late 40s. She was the first person officially diagnosed with Alzheimer’s disease. Many people with Alzheimer’s only start to show symptoms of this disease in their mid-60s or later, which accounts for over 95% of all cases and has a complex etiology. Although scientists haven’t found a specific gene that directly causes late-onset Alzheimer’s, it has been scientifically proven that having the apolipoprotein E (APOE) gene –– specifically APOE ε4 –– increases a person’s risk of developing Alzheimer’s disease, although this correlation does not imply causation. At the beginning stage of AD, Alzheimer’s destroys neuron connections in the brain that involve memory –– the entorhinal cortex and hippocampus. This will also cause damage in other areas of the brain, including the cerebral cortex, causing the person to lose the language, reasoning, and social behavioral functions of their brain. This occurrence continues to cause widespread damage around the brain, and brain tissues begin to shrink. By its final stage, brain atrophy causes a significant loss of brain volume. Brain atrophy is a process that occurs when all of the brain has shrunk and this leads to decreased functions that the brain controls, which goes to show how fatal Alzheimer’s disease is.

The most prominent molecular and cellular changes that occur in Alzheimer’s disease and

dementia, in general, can be associated with amyloid-beta and neurofibrillary tangles. These molecular and cellular changes that go inside the brain occur when abnormal levels of a naturally occurring protein called Amyloid Beta (Aβ), a peptide derived from amyloid precursor protein (APP), are clumped together to form amyloid plaques, which causes the symptoms appearing in Alzheimer’s disease. One form that it can come in is beta-amyloid 42, disrupting cell function and ultimately leading to cell death, which proves this protein is extremely toxic to the human brain. On the other hand, neurofibrillary tangles are another type of abnormal accumulation of a malignant protein called Tau that collects inside neurons in an insoluble form. In Alzheimer’s, chemical abnormalities disrupt the synaptic communication between neurons, causing the protein to detach from microtubules and conjoin with other Tau molecules that tangle the neurons. Misfolded Tau proteins can spread into healthy neurons, where healthy Tau protein starts to misfold as well, thus spreading pathology across the brain.

In recent years, scientists and doctors have made progress in better understanding Alzheimer's

disease and they have developed new treatment paths, including medications that are currently tested in late-stage clinical trials. On June 7, 2021, the newest medication for treating Alzheimer’s disease ––

aducanumab was approved by the U.S Food and Drugs Administration (FDA) to put into use for

Alzheimer’s patients and this drug aid the brain by reducing the production of amyloid plaques in order to slow down the progression of Alzheimer’s disease. It achieves this by breaking down protein

beta-amyloid aggregates in the brain into smaller proteins: amino acids or oligopeptides. Aducanumab is the only disease-modifying medication currently approved to be prescribed to Alzheimer’s patients. This medication is injected into the patient intravenously (infused through a vein) on a monthly basis. Like most medicines, aducanumab is most used effectively in the early or middle ages of Alzheimer’s disease. However, there are no available medicines at this time that can cure Alzheimer’s.

In current clinical trials, scientists are testing out immunization therapy, drug therapies, and the combination of cognitive training and physical activity to treat Alzheimer’s disease. One of the most

effective approaches is to utilize anti-amyloid beta immunotherapy to treat Alzheimer’s patients. Currently, the mostly used approach of immunotherapies are vaccines and exogenous antibodies, also

known as active and passive immunotherapy. AN-1792 was the first active anti amyloid beta vaccine that was developed, it contains full-length Aβ peptide and it has shown success in reducing Aβ plaque

formations in the brain. Another example includes the CAD106 vaccine, this active immunotherapy has the benefits of long-lasting antibodies at a limited cost. However, it is difficult to predict the immune responses in patients, especially for elderlies, which may cause complications. On the other hand, the combination of cognitive training and physical activity is proven to be effective for cognitive impairment, which enhances memory consolidation and performance of memory retrieval for people with mild Alzheimer’s disease or vascular dementia. This method aids in helping patients in the early stages of dementia, to better understand these links between their thoughts, feelings, and behaviors to improve brain performance.

For treating patients showing mild to moderate Alzheimer’s symptoms, drugs such as

galantamine, rivastigmine, and donepezil –– all of which are cholinesterase inhibitors, are prescribed to Alzheimer’s patients to help control some cognitive or behavioral symptoms. Cholinesterase inhibitors help break down acetylcholine –– a brain chemical that plays a crucial role in the brain’s memory and learning, acting as a neurotransmitter. However, as Alzheimer’s progresses, the brain produces less and less acetylcholine, and these medicines eventually lose their effect. All of these medications have potential side effects, which include nausea, vomiting, diarrhea, allergic reactions, and more. This explains why doctors usually prescribe patients low drug doses at first and gradually increase the dosage depending on the patient’s tolerance.

Although we are still in the works of clinical trials and there are no current treatments that can

fully cure Alzheimer’s disease, scientists are currently exploring a variety of ways not only to treat

symptoms of Alzheimer’s disease but also aiming to address its underlying disease processes. These

methods include the different immunotherapies, drug therapies, cognitive training, and physical activities tested in clinical trials as mentioned above that are proven to be helpful for the treatment process, and these scientific discoveries will hopefully aid in the betterment of developing more effective treatment paths for Alzheimer’s disease in the future.