In a recent study, researchers at Washington University School of Medicine achieved a significant breakthrough by transforming ordinary skin cells into neurons. This innovative process offers unprecedented insights into late-onset Alzheimer’s disease by closely replicating the protein build-up that is characteristic of the condition. By mimicking this aspect of Alzheimer’s with remarkable accuracy, the study not only enhances our understanding of the disease's progression but also reveals previously hidden information about the mechanisms underlying late-onset Alzheimer’s. This discovery could pave the way for new research approaches and potential treatments for this debilitating condition.
To fully appreciate the impact of this study, it's important to understand the nature of Alzheimer's disease, particularly the late-onset form that affects so many individuals. Alzheimer's is a type of dementia that is a general term for memory loss and regression of other cognitive abilities serious enough to interfere with daily life. The term called late-onset Alzheimer’s (LOAD) refers to Alzheimer’s disease that develops when someone is 65 years old or older. Around 90-95% of people with Alzheimer's develop it after 65 years, and about 1 in 9 people aged 65 or older has Alzheimer’s.
The brain changes that lead to late-onset Alzheimer's start occurring years before the first symptoms appear. Modeling Alzheimer’s disease is crucial to understand the pathophysiology of the disease and identify effective therapies. Occasional, non-genetic and late-onset Alzheimer’s disease (LOAD) is the most common form, but unfortunately, LOAD models are lacking due to the complexity.
To address this problem, researchers at Washington University School of Medicine in St. Louis have developed a way to capture the effects of aging on the development of Alzheimer’s disease. They have devised a method to study aged neurons in the lab without a brain biopsy, an advancement that could contribute to a better understanding of the disease and new treatment strategies. The scientists took skin cells from patients with LOAD and transformed them into brain cells called neurons. For the first time, these lab-derived neurons accurately reproduced the hallmarks of this type of dementia. These findings not only deepen our understanding of Alzheimer’s but also suggest potential new treatment strategies targeting these elements.
Until this major discovery, the studies were mostly done on animals, specifically mice with rare genetic mutations known to cause inherited, early-onset Alzheimer’s in younger people. This method sheds light on this disease but it’s not fully accurate for its late-onset form. Andrew Yoo and his team developed an approach called cellular programming to solve this issue.
The method enables the study of LOAD to be less risky as it does not use a brain biopsy. The risks of brain biopsy include bleeding, brain swelling, seizures, and more, so a study method that doesn’t include these risks is significant for a safer and better examination.
“It has been tough to study in the lab due to the complexity of the disease stemming from various risk factors, including aging as an important contributor. Until now, we did not have a way to capture the effects of aging in the cells to study late-onset Alzheimer’s.” said senior author Andrew Yoo, PhD, a professor of developmental biology. As told by Professor Yoo, this study made a significant impact on examining and developing treatment methods for LOAD, which represents more than 95% of Alzheimer’s cases.
The researchers also found that when skin cells are turned into neurons, they can grow a thin layer of gel that looks and acts like the 3D environment of the brain. During this process, certain genes linked to inflammation became active, which led to the neurons starting to die. This closely mimics what is seen in brain scans of patients with neurological diseases. This finding is important because it helps scientists better understand how these diseases progress and provides a useful model for testing potential treatments.
Through these results, researchers were able to find drugs that interfere with the formation of protein build-up early in the disease process. However, after a certain level of protein build-up, treatment has little to no effect. Such data emphasize the importance of identifying and treating the disease early.
The team paved the way for other researchers to conduct low-risk and accurate examinations, as well as to develop drugs that can lower the symptoms of Alzheimer’s disease. This recent study is a groundbreaking step in the world of neuroscience and will impact hundreds of people’s lives in the future.