June 23, 2026

@michaelokun

Can genetics and brain pathology finally explain why Parkinson's is not one disease? Pathology refers to what is actually happening in the brain under the microscope. Co-pathology means more than one disease process occurring in the same brain at the same time. Wu and colleagues describe in a new paper in JAMA Neurology one of the largest global brain bank studies ever assembled, combining genetics, pathology, and clinical data from more than 3,300 individuals with Parkinson's disease and related disorders. Key points: - Clinical misdiagnosis remained common, occurring in approximately 10-20% of movement disorder cases even in expert centers. - Alzheimer’s disease co-pathology was present in 40% of Lewy body disease cases, highlighting that dementia in Parkinson's is frequently driven by multiple disease processes. - GBA1 carriers had more extensive Lewy body pathology, while LRRK2 carriers showed less Lewy pathology and longer survival, revealing important biological differences between genetic forms of Parkinson's disease. My take: This study reinforces a message that neuropathologists have been teaching us for decades. Dementia, Parkinson's disease, Lewy body disease, PSP, MSA, and corticobasal syndromes are frequently not clean diagnostic boxes. The brains tell a more complicated story. What struck me most was that 40% of Lewy body disease cases also harbored significant Alzheimer pathology. The future of precision medicine will require us to move beyond labels and toward defining the biology actually occurring in each individual brain. Studies like this help explain why some therapies succeed, why others fail, and why two folks carrying the same diagnosis may experience very different journeys. Here are 3 points that resonated w/ me: 1- Parkinson's disease is frequently accompanied by other brain pathologies, especially Alzheimer-related changes. 2- Clinical diagnosis remains imperfect, emphasizing the urgent need for better biomarkers during life. 3- Genetics matters. GBA1 and LRRK2 Parkinson's disease may represent biologically distinct forms of the disorder.