A recent study conducted by scientists sheds light on how boosting mitochondrial energy output may halt the progression of Alzheimer’s disease. The brain heavily relies on energy to facilitate the communication between nerve cells, which is essential for thoughts, memories, and emotions. However, in Alzheimer’s patients, this vital energy source begins to falter, leading to a decline in cognitive function.
The study, published in Advanced Science by researchers at Scripps Research, delved into the intricacies of cell machinery, particularly focusing on mitochondria – the powerhouse of cells responsible for keeping neurons active and healthy. By addressing the malfunctioning mitochondria in nerve cells derived from Alzheimer’s patients, the researchers observed a significant improvement in the connections between neurons.
The breakdown of mitochondrial health has long been associated with neurodegenerative diseases, with a strong correlation found in Alzheimer’s disease. When these cellular engines malfunction, cognitive decline becomes evident. Specifically, the study highlighted a disruption in the Krebs cycle due to a chemical change known as S-nitrosylation, which affects key proteins involved in energy production.
The researchers identified a surge of damaged proteins in Alzheimer’s brains, termed as a “SNO-Storm,” which impairs energy production at its core. By utilizing advanced techniques to measure oxygen consumption rates, deficits in the TCA cycle were pinpointed in both postmortem Alzheimer’s brains and neurons derived from patient stem cells.
The study also revealed a bottleneck in the production of succinate within the Krebs cycle, crucial for generating ATP – the primary energy source for cells. Restoring succinate levels was hypothesized to enhance energy production, offering a potential avenue for restoring cognitive function in Alzheimer’s patients.
Researchers encountered challenges in crossing nerve cell membranes to address decreased synapses in Alzheimer’s nerve cells. By utilizing a succinate analog that effectively penetrates cells, they successfully restored up to 75% of lost synapses in their models, offering a potential route to enhance neuronal connectivity. Dr. Stuart Lipton, the study’s senior author, highlighted the proof-of-principle for re-energizing the Krebs cycle with succinate, emphasizing the crucial need for further research to develop safe and efficient energy-restoring drugs for humans.
The implications of this research surpass the laboratory setting, with Dr. Lipton emphasizing mitochondrial metabolism as a promising therapeutic target for Alzheimer’s and related neurodegenerative disorders. The study emphasized the significance of understanding energy deficits in Alzheimer’s, with posttranslational modifications like S-nitrosylation playing critical roles in bioenergetics. The researchers utilized human-induced pluripotent stem cell (hiPSC) models to study Alzheimer’s at the cellular level, generating neurons from patient-derived stem cells to identify disease-related metabolic changes and therapeutic targets accurately.
While the findings provide hope, the road to an effective treatment for Alzheimer’s remains challenging. Developing drugs to safely restore mitochondrial function will require rigorous testing and clinical trials. Given the complexity of Alzheimer’s, addressing energy deficits may need to be combined with other therapeutic strategies to tackle the multifaceted nature of the condition. Dr. Lipton’s team is dedicated to advancing this research to target the energy crisis in the brain, aiming to halt disease progression and enhance cognitive outcomes for patients.
Amidst an environment where Alzheimer’s disease affects millions globally, breakthroughs like these offer hope for combating the condition through scientific innovation and compassion. By preserving neurons and their connections, researchers are paving the way for treatments that can help maintain memories and independence in individuals affected by Alzheimer’s.
Alzheimer’s disease is less common, but the number of people living with it doubles every 5 years past age 65. By 2060, it’s projected to almost triple to 14 million. Symptoms typically appear after age 60, with risk rising with age. Scientists are still unraveling the causes, likely a mix of factors affecting individuals differently. Age and genetics play roles, but a healthy lifestyle can help lower the risk. Brain changes can start years before symptoms, and research examines links to education, diet, and environment. Healthy habits proven to prevent other diseases may also reduce Alzheimer’s risk.
In the US, Alzheimer’s ranks among the top 10 causes of death, 6th overall and 5th among adults 65+. In 2020, around 5.8 million Americans 65+ had the disease, set to triple by 2060. Treatments costs are projected to soar from $159-215 billion in 2010 to $379-$500 billion annually by 2040. Unlike heart disease and cancer, Alzheimer’s death rates are rising. Dementia, including Alzheimer’s, is often underreported on death certificates, possibly leading to higher actual rates.
