TL;DR Science: Alzheimer's Disease

What is Alzheimer’s disease? To understand it, we must first understand dementia. Dementia is the general term to describe memory loss that is severe enough to deter an individual from going about their daily life. Alzheimer’s disease is the most common cause of dementia.

Some Statistics

 Alzheimer’s disease affects:

o   more than 40% of individuals over the age of 85

o   Nearly 20% of people aged 75 to 84

• 5 million Americans may have Alzheimer’s disease
• By 2040, Alzheimer’s disease is predicted to affect approximately 14 million individuals in the United States.

Symptoms of Alzheimer’s disease

Alzheimer’s disease’s earliest symptoms include forgetfulness; difficulty with concentration, calculation, language, judgment; and disorientation to time or place. As the disease progresses, patients may have severe mood and behavioral disturbances, suspicions about family, friends, and caregivers, difficulty speaking, swallowing, walking, and may even become psychotic. In the final stages of Alzheimer’s, the individual becomes bed-bound. Patients typically die from pneumonia or complications from immobility that results from Alzheimer’s. 

The Science Behind Alzheimer’s 

The prime suspects that cause this debilitating disease are plaques and tangles. Plaques are deposits of a small fibrillar peptide known as beta-amyloid that builds up in the spaces around synapses. Synapses are the spaces between neurons, which is a nerve cell. Tangles are abnormal accumulations of a protein called tau in the cell bodies of neurons. 

Although most people develop plaques and tangles to some extent as they age, individuals with Alzheimer’s tend to generate far more in brain regions that are crucial for memory and intellectual functions. There is still very little that we know about the role plaques and tangles play in Alzheimer’s disease. However, most scientists believe that the plaques and tangles play a critical role in blocking communication between neurons, which leads to the inability of neurons to carry out the processes that ensure their survival. 

Early-onset Alzheimer’s disease occurs in individuals under the age of 65. It is a rare, dominantly inherited form of the disease. Researchers have recently identified the mutations associated with early-onset Alzheimer’s. The first is a gene that encodes the amyloid precursor protein on chromosome 21. The amyloid precursor protein plays an integral part in the formation of beta-amyloid. The second mutation identified is in the presenilin 1 and 2 genes. Presenilin cuts apart the amyloid precursor protein, which results in beta-amyloid. Different lengths of beta-amyloid are associated with Alzheimer’s. 

This is a diagram that compares a healthy brain to one with advanced Alzheimer’s. The brain on the right has clearly shrunk. Due to the abnormal amount of plaques and tangles in the brain, there are fewer connections between neurons. 

Treatments:

To this day, there is no known cure for Alzheimer’s. Current treatments focus on slowing down the progression of symptoms and maintaining mental functions. While most patient treatments are approached on a case by case basis, the following are some common ones:

Music Therapy:

Music therapy has presented itself as an unorthodox treatment for Alzheimer’s patients. The main reason why this therapy is effective is because research has indicated that the memory of music is mostly unaffected by the cognitive degradation associated with Alzheimer’s. The current theory on why this is the case is that the memory networks for music are separate from other memory networks of the temporal lobe and the fact that music memory/processing is not localized to any one area of the brain.

Music therapy is also effective in that behavioral studies have shown that music may improve Alzheimer’s patients’ cognitive function. The study conducted by Foster and Valentine in 2001 showed that background music can help one’s autobiographical recall. Music also can trigger the recall of emotional memory. A study conducted by de la Rubia Ortí showed that music could help reduce stress levels and improve a patient’s emotional state.

Most importantly, it helps that music therapy is enjoyable, meaning that patients are much more unlikely to refuse this treatment than other conventional therapies. In early-stage Alzheimer’s patients, playing music itself might be something that they find pride in, providing a significant boost to their emotional and mental well-being.

Interestingly enough, there are a few songs that have been consistently selected as favorites by Alzheimer’s patients, which include:

“Moon River,” by Andy Williams,

“You Are My Sunshine,” by Jimmie Davis,

“Singing in the Rain,” by Gene Kelly,

“The Way You Look Tonight,” by Frank Sinatra,

“All Shook Up,” by Elvis Presley,

“Que Sera Sera,” by Doris Day

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This is a video about a woman named Ruth whose disease has progressed to the point where she can’t remember her daughter’s name. However, we can see the beauty of music and the effect it has on her. 

Aducanumab:

In 2015, a Cambridge-based biotech company, Biogen, began rising in popularity thanks to its work on a potential ‘cure’ for Alzheimer’s. Many called it [the] “first real treatment” for the brain disease. After performing initial trials, Biogen published results for their treatment, Aducanumab. 

Dr. Dennis Selkoe, professor of neurologic diseases at Brigham and Women’s Hospital and Harvard Medical School, said, “I think there’s a reasonable chance that Aducanumab, if approved and we don’t know that yet, will be the first disease-modifying agent for Alzheimer’s, and that will be a huge milestone and patients of mine and others can access the drug.”

Previously, doctors could only offer treatments that would slow the progression of the disease. Thanks to the work at Biogen, Aducanumab alters the Alzheimer’s course, offering a real solution.

An article at the WBUR CommonHealth states, "Aducanumab is an antibody. It binds to the amyloid-beta protein, especially aggregate forms of the amyloid-beta protein that we consider to be the principal bad guys in Alzheimer’s disease. Alzheimer’s begins in many cases, if not most cases, with the build-up of this small protein called amyloid-beta and the formation of amyloid-beta plaques. There’s a lot of evidence that people with too much build-up of this small protein develop Alzheimer’s. Now, aducanumab binds to amyloid-beta protein. It mobilizes the body’s immune system against the amyloid-beta plaques and seems to clear the plaques themselves.”

"The next step in Alzheimer’s is the buildup of toxic tangles of a protein called tau, as well as the accumulation of tau in an abnormal form called phospho-tau. In participants in Biogen’s clinical trials, amyloid plaque burden went down, and tau burden went down.”

"Importantly, in the phase three clinical trials, Aducanumab helped the rate of decline of cognition in patients — things like memory and other cognitive functions that are lost gradually. Evidence that Aducanumab helped preserve doing household chores, cleaning, preparing a little food, and doing other everyday tasks that we expect folks to do relative to placebo. Aducanumab blunted that decline. It didn’t stop the decline, but it slowed it, which is what we’re hoping for."

The FDA voted ‘No’ to Approving Aducanumab in a December 2020 meeting. They cited a lack of consistent data as the primary concern. On February 4th, 2021, the approval decision for the drug was delayed for three months. All eyes will be on the FDA this May, hoping for a clear conclusion.

TL;DR Alzheimer’s disease is a debilitating disease that affects not only the patient but also those around them. While our current treatment options only work on decreasing the spread of symptoms, future treatments are making an Alzheimers-free world a possibility. 

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