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Could Malfunctioning Mitochondria Predict Alzheimer’s Disease?

QPS Neuro

Alzheimer’s Disease, or AD, is an incurable neurodegenerative condition that generally appears in individuals over the age of 65. However, scientists now believe that certain predictors can appear in a patient’s brain decades before symptoms appear — specifically, malfunctioning mitochondria. With that in mind, researchers at the European Synchrotron Radiation Facility (ESRF) recently posed an exciting question: Could malfunctioning mitochondria be an accurate predictor of AD?

Understanding AD Origins

Alzheimer’s disease impacts millions of people around the world — and yet, the origins of the illness still aren’t fully understood. For decades, researchers have explored the presence of amyloid plaques, which are abnormal proteins in the brain, as a potential cause of the disease. But now, new research published in Nature Communications by the ESRF goes a step further, suggesting another focus: the mitochondria within brain cells.

The Role of Mitochondria in AD Development

To begin their research, the team focused on mitochondrial dysfunction in aging individuals. Mitochondria, sometimes referred to as the “powerhouse” of the cell, play an important role in cellular energy production, but they are known to malfunction over time, largely due to stress when physical antioxidant levels are low. As seen in individuals with AD, inefficient cellular energy production can be devastating.

But what if mitochondria malfunctioned for a different reason? The ESRF team suspected that individuals with AD may experience the presence of amyloids, the aforementioned abnormal plaques, within their mitochondria. That plaque buildup could compromise the key protein complexes necessary to generate sufficient energy within brain cells, potentially predicting AD as a degenerative condition.

Exploring Mitochondrial Malfunction

Like many biological components, mitochondria rely on proteins called assembly factors to generate energy efficiently. The research team honed in on one assembly factor complex known as mitochondrial complex I assembly (MCIA), which consists of three core proteins: ECSIT, ACAD9, and NDUFAF1. They then mapped the structure of that protein complex using cutting-edge cryo-electron microscopy. At that point, they discovered that ECSIT plays an important role in coordinating crucial cellular energy mechanisms. Finally, they concluded that ECSIT can become compromised in the presence of amyloids, resulting in overactive and inefficient energy generation. The head researcher noted that the process creates “a detrimental cycle that eventually leads to the impairment of the respiratory chain” in the mitochondria, thereby setting the stage for the onset of conditions like AD. This observation upends previous assumptions about the link between amyloids and the development of AD.

Mapping the structure of something as tiny as the mitochondria within a cell might seem overly minute; however, clinical research projects like this one demonstrate just how important the tiniest cellular components can be for breakthrough medical research. Ultimately, this highly targeted research could pave the way for a better understanding of the early stages of Alzheimer’s. Once researchers are able to identify the factors that drive the disease, they could be one step closer to delaying its onset and slowing its progression, potentially changing the lives of millions.

QPS Neuropharmacology is a division of QPS, a GLP/GCP-compliant contract research organization (CRO) delivering the highest grade of discovery, preclinical, and clinical drug development services since 1995. QPS Neuropharmacology focuses on preclinical studies related to central nervous system (CNS) diseases, rare diseases, and mental disorders. With highly predictive disease models available on site and unparalleled preclinical experience, QPS Neuropharmacology can handle most CNS drug development needs for biopharmaceutical companies of all sizes. To study conditions like Alzheimer’s disease, QPS Neuropharmacology offers several in vitro and in vivo models and related behavioral, histological and biochemical analysis methods. For more information about QPS, visit www.qps.com, and for more information about QPS Neuropharmacology, visit www.qpsneuro.com.