Exploring the Role of Mitochondrial Dysfunction as a Key Contributor to Alzheimer’s Disease

Alzheimer’s disease (AD) is a complex neurodegenerative disorder affecting over six million Americans. For decades, the prevailing hypothesis about the root cause has been that the accumulation of beta-amyloid plaques in the brain is the primary driver of cognitive decline in AD. However, recent research has cast doubt on this theory. 

In fact, a growing body of evidence suggests that mitochondrial dysfunction may play a pivotal role in the development and progression of Alzheimer’s disease, challenging the conventional beta-amyloid hypothesis.

Let me explain why this is significant and share some insights from an article I read on Big Think:

The first thing you need to know is that mitochondria are responsible for various cellular functions, including metabolism, oxidative stress regulation, and cell death. Mitochondrial dysfunction occurs when these organelles cannot produce ATP and maintain cellular homeostasis efficiently. This dysfunction can lead to oxidative stress, impaired calcium regulation, and inflammation – all of which are observed in the brains of Alzheimer’s patients. 

The amyloid accumulation hypothesis has dominated Alzheimer’s research for a long time, proposing that the build-up of beta-amyloid plaques is the initiating event in the disease process. These plaques are believed to disrupt neuronal communication, leading to cognitive decline and memory loss. However, clinical trials targeting these plaques have not yielded the expected results, prompting researchers to consider alternative explanations for Alzheimer’s pathology. 

One of the most promising alternative explanations deals with mitochondrial dysfunction  because it impairs the brain’s ability to produce energy, contributing to neuronal dysfunction and cognitive decline. Mitochondrial dysfunction also increases reactive oxygen species (ROS), causing oxidative stress that damages cellular components, including proteins, lipids, and DNA. Not surprisingly, oxidative stress is a hallmark of Alzheimer’s and contributes to neuroinflammation and neuronal death. 

Another important thing to note is that mitochondria play a vital role in regulating calcium levels within neurons. When calcium homeostasis is disrupted, it can lead to neuronal dysfunction and cell death, characteristic of Alzheimer’s pathology. Tau protein aggregates have also been found to impair mitochondrial function. This creates a vicious cycle, where mitochondrial dysfunction promotes tau pathology, and tau aggregates further compromise mitochondrial function. 

All of this evidence is pointing to mitochondrial dysfunction being a driving force behind Alzheimer’s development. However, instead of being an independent phenomena, mitochondrial dysfunction and beta-amyloid accumulation may be interconnected processes. In other words, mitochondrial dysfunction could be an early event contributing to beta-amyloid aggregation, setting off neurodegenerative processes. 

At PUR-FORM we have a variety of ways we can help boost mitochondrial health, including NAD+ treatments that are critical for optimal mitochondrial function.

And if you’re looking for ways to boost mitochondria at home, read my post here:

How High Intensity Interval Training Generates Significant Increases in Mitochondria

Joseph Purita, MD