Wow! New paper @NEJM showing that biomarkers are changing in Alzheimer's 6-18 years before clinical symptoms appear and a diagnosis is made. Key Points: - 648 participants and 648 controls. - Median follow-up was ~20 years and here is what the authors detected BEFORE SYMPTOMS AND DIAGNOSIS. - Amyloid-beta (Aβ)42 at 18 years - The ratio of Aβ42 to Aβ40 at 14 years - Phosphorylated tau 181 at 11 years - Total tau at 10 years - Neurofilament light chain at 9 years - Hippocampal volume at 8 years - Cognitive decline at 6 years My take: This dataset is humbling but not surprising. Neurodegenerative changes in both Parkinson's and Alzheimer's are known to occur many years prior to obvious 'clinical' symptoms and symptoms that can be detected by bedside and neuropsychological testing. This information is useful as we further development of early screening tests and improved neurotherapeutics. Scientists love to talk about 'a priori' - from what comes before. Well, here you go.... nejm.org/doi/full/10.1056/NE… #Parkinsons #Alzheimers #biomarkers