Week 3: Turning Up The Volume In Discovery

Kelin X -

Salutations, music and brain lovers! Welcome back to another weekly blog post about my senior project! I hope you all are doing well, and I appreciate you guys just riding along with me on my journey! I figured to dedicate this blog post mostly, if not all, about my research so far on Alzheimer’s Disease (AD) itself instead of talking more about my observations I’ve had this week so far and about how other neurological and/or neurodevelopmental disorders tie into what I’m mainly studying. I might add in some specific information about music on different aspects of AD at the end of this post. Let’s get into one small chunk of the very cool information I’ve learned about Alzheimer’s. I hope you all are as excited as I am to get down into a fraction of the neuroscience behind it all.

For starters, if I haven’t already said this, I’d like to give you a proper introduction to Alzheimer’s Disease. As you may or may not already know, Alzheimer’s is the most common cause of dementia, accounting for 60–80% of cases. AD is a continuously progressive neurodegenerative disorder characterized by progressive memory loss, cognitive decline, and changes in behavior. At the core of this deterioration is the buildup of amyloid-beta plaques (protein deposits that form in the spaces between nerve cells in the brain) and neurofibrillary/tau tangles (abnormal accumulations of the protein tau that form in nerve cells in the brain), which disrupt neural communication and lead to widespread brain atrophy (a gradual decline in the size and volume of the brain; it occurs when brain cells (neurons) die or lose their connections, resulting in a shrinkage of the brain tissue). The hippocampus, a region crucial for memory formation and retrieval, is one of the first areas affected, leading to the hallmark symptom of forgetfulness. Symptoms often begin with mild memory loss and gradually progress to severe impairment in reasoning, language, and daily functioning; these can be quite devastating effects. This isn’t a not-so-fun fact but currently, Alzheimer’s affects over 55 million people worldwide, a number expected to rise as life expectancy increases and the fact that our global population is just aging.

So…you may be asking at this point: what are some risk factors, factors believed to contribute to AD’s development? Well to answer your question, examples include age, family history, genetics, head injury, certain medical conditions already present, vascular disease (conditions such as high blood pressure, stroke, and heart disease that can damage blood vessels in the brain), environmental factors, lifestyle factors, and more.

Furthermore, researchers haven’t found a single gene solely responsible for Alzheimer’s disease; rather, multiple genes are likely involved. One genetic risk factor—having one form of the apolipoprotein E (APOE) gene on chromosome 19—does increase a person’s risk for developing AD. People who inherit one copy of this APOE ε4 allele have an increased chance of developing the disease; those who inherit two copies of the allele are at even greater risk. In case you don’t know or you forgot, an allele is a variant form of a pair of genes that are located on a particular chromosome and control the same trait. The APOE ε4 allele may also be associated with an earlier onset of memory loss and other symptoms. Researchers have found that this allele is associated with an increased number of amyloid plaques in the brain tissue of affected people.

Despite ongoing research, there is sadly still no cure today, but medications and management strategies may temporarily reduce the symptoms. However, music therapy is a non-invasive, therapeutic tool to help Alzheimer’s/Dementia people navigate through their ups and downs of their condition. Research has continued to emphasize that music—particularly tempos, rhythms, and frequencies—can serve as a powerful tool for memory retention and cognitive stimulation in individuals with AD. Music has a unique ability to activate multiple brain regions simultaneously, engaging not only the auditory cortex but also the limbic system (responsible for emotions) and the prefrontal cortex (associated with decision-making and attention). Even when verbal memory fades, musical memory often remains intact, allowing patients to recall melodies, lyrics, and emotions associated with songs from their past; it’s such a beautiful and precious thing. Neuroscientific studies suggest that musical interventions can enhance synaptic plasticity (neuroplasticity), the brain’s ability to reorganize and form new neural connections. This is crucial in AD, where neuronal networks are continuously breaking down. When a familiar song plays, it can trigger the recall of associated memories and emotions, providing a sense of identity and comfort for patients. This process occurs through the activation of the medial prefrontal cortex, an area that remains relatively preserved in AD until the later stages. Now let’s talk about the role of genre, tempo/rhythms, and frequency within music. To address the questions already asked in my week 2 blog post and any other potential questions that I’ll receive this week regarding how the components of music affect AD clients…when it comes to genre, there’s no particular one that’s more effective at engaging the brain and yielding positive results; however, usually compositions with slower tempos and harmonic progressions, have been shown to reduce agitation and improve mood in AD patients. The works of Mozart, Bach, and Debussy, for example, are often used in music therapy due to their calming effects and ability to engage higher cognitive functions. Memory retrieval is strongest when music from an individual’s formative years is played. For many Alzheimer’s patients, familiar songs from their early life evoke strong emotional and cognitive responses. As for rhythm/tempo… Slow to moderate tempos (60–80 beats per minute) can promote relaxation and cognitive engagement, whereas faster tempos (above 100 BPM) may stimulate movement and encourage physical activity, benefiting motor function. As for frequencies…high sounding and low sounding ones can both be beneficial but just in different ways; they make AD patients feel differently, as high frequencies tend to be more stimulating and provide alertness whereas low frequencies tend to be more soothing and for relaxation purposes. Some studies though suggest that 40 Hz auditory stimulation can enhance gamma wave activity in the brain, potentially reducing amyloid buildup and improving cognitive function in AD patients.

Just for additional information, in case you’re curious, Alzheimer’s disease is named after Dr. Alois Alzheimer. In 1906, Dr. Alzheimer noticed changes in the brain tissue of a woman who had died of an unusual mental illness. Her symptoms included memory loss, language problems, and unpredictable behavior. After she died, he examined her brain and found many abnormal clumps (now called amyloid plaques) and tangled bundles of fibers (now called neurofibrillary, or tau, tangles). This is how amyloid-beta plaques and tau tangles became 2 of the most significant and defining features of AD.

That’s all I have for you guys for this week. As always, feel free to leave any comments asking me any questions you may have! I’m always here for clarification and your wonderful insights! May your neurons keep firing and your melodies keep inspiring!

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    helga_a_l
    Hello, Kelin! Your senior project is such an interesting topic! Music and neuroscience were always interests of mine, and learning how they are combined to create effective treatments is fascinating. I was wondering if you could elaborate more on the amyloid-beta plaques and tau tangles. Specifically, you mentioned that abnormal buildup of both these leads to Alzheimer's, so I was curious if they had any beneficial functions if regulated and maintained in lower levels in the brain. Thank you for the great update!
    Jolie L
    Hi Kelin !! Your post is very informational!! Keep up the great work :D. I do have a question though, how common is the apolipoprotein E allele?
    Alisa Udachina
    Hi, Kelin!!! You are doing a PHENOMENAL work!!! 😎😎😎Your detailed exploration of Alzheimer’s Disease and its connection to music therapy is fascinating. I’m particularly intrigued by how music can evoke memories and emotions even when other cognitive functions decline. Are there any specific studies or findings that have particularly inspired your research?🤩😝╰(*°▽°*)╯
    Roberto D.
    Hello! You mentioned that APOE ε4 is an allele, my question is if the allele is dominant or recessive? Is the genetic risk factor the most common risk factor for alheimzers or are the others such as brain injury or age more common?
    Akshaya Madhankumar
    Hi Kelin! Does the activation of multiple brain regions while listening to music have a positive effect on the formation of the amyloid precursor protein in those areas/neural connections? I’m so excited to see how your project turns out!
    Kelin Xu
    Hello, Helga! I also think your senior project on OCD is intriguing! It's great to know that music and neuroscience are also a few interests of yours! Thank you for your sweet comment and good question. As for further elaboration on amyloid-beta plaques and tau tangles, I'm planning on including more information about them in my upcoming blog post; however, to simply put it...amyloid-beta plaques (abnormal clumps of protein fragments) originate from the amyloid precursor protein (APP), a normal protein found in the brain. In Alzheimer’s disease, APP is improperly cleaved (split or sever), leading to the production of toxic Aβ peptides that aggregate into insoluble plaques. These plaques disrupt cell-to-cell communication, trigger inflammation, and promote oxidative stress, ultimately contributing to neuronal death. Now for tau tangles...tau is a protein responsible for stabilizing microtubules, which are essential for transporting nutrients and molecular signals within neurons. In Alzheimer’s disease, tau undergoes abnormal chemical modifications, causing it to detach from microtubules and aggregate into twisted fibers known as neurofibrillary tangles. This destabilization disrupts the internal structure of neurons, impairing their ability to function and communicate effectively. As tau tangles accumulate, neurons lose their structural integrity and eventually die, further contributing to brain atrophy and cognitive impairment. To address your curiosity...yes, both when regulated and maintained at lower levels contribute to essential brain functions. Information regarding those brain functions should be included in this week's blog post. Feel free to check it out when it's posted!
    Kelin Xu
    Hi, Jolie! I really appreciate your interest, encouragement, and sweet remarks! Thank you so much! The Apolipoprotein E (APOE) gene has three major alleles: ε2, ε3, and ε4, with APOE-ε4 being the most significant genetic risk factor for late-onset Alzheimer's Disease (AD), as you already know. The ε3 is found in approximately 78% of the population globally, while the ε4 is present in around 14-20% of the general population, but its presence increases the risk of developing AD. Having one copy of ε4 increases risk by about 2-3 times, while having two copies (homozygous) increases risk by 12 times or more. At least that's what I've read somewhere throughout my research. ε2 is the least common allele, present in about 8% of people, and is thought to have a protective effect against AD.
    Kelin Xu
    Hey, Alisa!!! Thank you so much for your enthusiasm and support! Your very sweet comments mean so much to me! I'm also fascinated by how music can evoke precious values like memories and emotions even when some cognitive functions just aren't as strong. It's nice that we share that interest. Yeah, there are several interesting sources that I've been using for my research on my topic, and I definitely consider them to be inspirational! Sources like TED Talks, information posted in the Alzheimer's Association page, and articles/studies from the NIH are just a few examples that I find to be driving my research forward. Thanks for your good question!
    Kelin Xu
    Hello, Roberto! You asked a really good question, and thanks for asking! APOE ε4 is neither strictly dominant nor recessive—it's a risk factor allele, meaning it increases the likelihood of developing Alzheimer’s disease but does not guarantee it. The risk increases depending on the number of copies inherited. One copy of APOE ε4 (heterozygous) roughly triples the risk, whereas two copies (homozygous) can increase the risk by 10–15 times compared to those without it. Many people with APOE ε4 may never develop Alzheimer’s, while some without it do thereby showing that other genetic and environmental factors can equally play a role. I would say though that the strongest risk factor for Alzheimer’s is age, as the likelihood of developing the disease doubles about every five years after age 65. As you already know, other significant factors include family history, cardiovascular health related issues (e.g., high blood pressure and high cholesterol), brain injuries, and lifestyle factors. While APOE ε4 is the most well-known genetic risk factor, age and lifestyle-related factors hold significant value and are actually more common in the general population.
    Kelin Xu
    Hey, Akshaya! I hope you're doing well, and thank you so much for your excitement on my senior project journey and for your great question! This might not be the answer you're looking for or expecting, but there actually isn't direct evidence that music influences the formation of the amyloid precursor protein (APP) itself, but what I've researched so far suggests that music engages multiple brain regions in ways that could affect Alzheimer’s pathology—particularly in relation to amyloid-beta (Aβ) accumulation, synaptic health, and neuroplasticity. Some studies I've read say that cognitive stimulation (including music) might reduce amyloid-beta buildup, which results from the cleavage of APP. Studies show that familiar music strengthens functional connectivity, which could slow down synaptic degradation. While music likely doesn’t directly alter APP formation, it may help regulate its processing, promote synaptic resilience, and reduce toxic amyloid effects. As a result, I'd assume that if there were any effect to happen, the activation of multiple brain regions while listening to music could likely leave a positive impact! I hope I answered your question!
    kelin_x
    Hi, Harshitha! I'm so sorry for my late response to your comment. It's really strange that I can't see your comment posted when I access my blog posts through the BASIS Ahwatukee Senior Project website. I just noticed your comment here in WordPress. Thank you so much for your interest and question, and I appreciate your patience in getting a response back from me! My answer to your question is that it's more so the familiarity of the music rather than a specific genre or tempo that triggers the memory "reaction" aspect of AD; however, if by "reactions" you mean the emotional response of a patient with Alzheimer's, then the higher frequency sounds are more stimulating which enhances alertness and engagement while the lower frequency sounds are more soothing which leads to relaxation and reduced anxiety and agitation. For physical reactions from patients, personalized music usually makes them tap or dance along. In short, AD patients respond best to music that was popular during their youth. I hope I answered your question!

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