Brain-first vs. body-first Parkinson's disease: An update on recent evidence

In a new disease model for Parkinson's disease, researchers suggest that the disease starts either in the smell-related area of the brain or in the gut nerves. These two types of starting points may show different symptoms early on. Recent studies using various techniques like brain imaging and clinical observations have mostly supported this model. They found that certain symptoms like sleep problems, digestive issues, and cognitive changes may indicate which subtype of Parkinson's disease a person has. Additionally, studies looking at brain tissue also support this idea. Parkinson's disease is a complex disorder with varying symptoms and outcomes among patients. It's characterized by the buildup and spread of a protein called -synuclein in the brain. Different models have been proposed to categorize patients based on their symptoms and disease progression. One model suggests that the disease starts in different locations in the body, leading to two main subtypes: brain-first and body-first. In the brain-first subtype, the disease starts in areas like the olfactory bulb or amygdala, while in the body-first subtype, it begins in the peripheral nervous system, likely the gut nerves, and spreads upward. This model helps explain why patients may experience different symptoms and progression patterns. According to the model, brain-first and body-first Parkinson's disease (PD) subtypes should have distinct clinical profiles, biomarkers, and imaging markers early in the disease. Brain-first PD typically shows more asymmetric motor symptoms, less impaired sense of smell, less autonomic dysfunction, and later onset of certain sleep disorders. In contrast, body-first PD often exhibits more symmetric motor symptoms, impaired sense of smell, along with autonomic problems and sleep disorders before motor symptoms appear. Other research groups have also investigated the SOC model and its subtypes, either by directly testing the model or by interpreting data within its framework. This review focuses on recent studies that provide evidence for or against the model's validity, using original human data. Most studies included in the review did not use the brain-first/body-first terminology but categorized PD patients based on relevant subtype-dependent markers. It's important to note that while the model focuses on -synuclein distribution, other factors like genetic risk, oxidative stress, and cellular dysfunction also influence disease progression and may vary among patients, posing challenges to reliably testing the model. This review looked at recent studies related to the SOC model and the brain-first/body-first subtypes of Parkinson's disease (PD). Most studies supported the model's predictions, but some had conflicting results, so more research is needed. To better understand these subtypes, future studies should focus on recruiting patients at early stages and track them over time using advanced imaging techniques like cardiac and dopamine imaging. They should also investigate how genetic and other risk factors relate to these subtypes. Identifying subtype-specific markers could help in diagnosing and treating PD more effectively. Additionally, finding ways to detect -synuclein in bodily fluids could be crucial for identifying brain-first PD patients early. Ultimately, with the development of better imaging tools, we'll have a clearer picture of how PD progresses and how to manage it.