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MDS 2021 | Questioning the Braak hypothesis in Parkinson’s disease

Alberto Espay, MD, FAAN, University of Cincinnati, Cincinnati, OH, talks on the Braak hypothesis of Lewy pathology progression in Parkinson’s disease (PD) and the need to reject it. The classical Braak hypothesis suggests that PD begins as a synucleinopathy in the lower brainstem or in the olfactory bulb which goes on to spread throughout the brain in a stereotyped pattern. Prof. Espay discusses the issues with the hypothesis noting that, based on the data gathered to date, there is no relationship between Braak stage and clinical severity of PD or the level of degeneration. There is also no support for a spread of Lewy pathology that precedes neurodegeneration and the onset of clinical symptoms. This interview took place during the 2021 International Congress of Parkinson’s Disease and Movement Disorders.


Prof. Espay has received grant support from the NIH and the Michael J Fox Foundation; personal compensation as a consultant/scientific advisory board member for Abbvie, Neuroderm, Neurocrine, Amneal, Acadia, Acorda, Kyowa Kirin, Sunovion, Lundbeck, and USWorldMeds; honoraria from Acadia, Sunovion, Amneal, USWorldMeds; and publishing royalties from Lippincott Williams & Wilkins, Cambridge University Press, and Springer. He cofounded REGAIN Therapeutics, owner of a patent application that covers synthetic soluble non-aggregating peptide analogs as a replacement treatment in proteinopathies. He serves on the editorial boards of the Journal of Parkinson’s Disease, Journal of Alzheimer’s Disease, European Journal of Neurology, and JAMA Neurology.