{"id":505033,"date":"2026-07-01T20:32:19","date_gmt":"2026-07-01T20:32:19","guid":{"rendered":"https:\/\/www.newsbeep.com\/nz\/505033\/"},"modified":"2026-07-01T20:32:19","modified_gmt":"2026-07-01T20:32:19","slug":"study-finds-little-to-no-cortical-lewy-pathology-in-living-parkinsons-disease-patients-undergoing-deep-brain-stimulation","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/nz\/505033\/","title":{"rendered":"Study Finds Little to No Cortical Lewy Pathology in Living Parkinson\u2019s Disease Patients Undergoing Deep Brain Stimulation"},"content":{"rendered":"

FOR IMMEDIATE RELEASE
Media Contact: Elizabeth Dowling
Mount Sinai Press Office
347-541-0212
[email\u00a0protected]<\/a>\u00a0<\/p>\n

Study\u00a0Finds Little to No Cortical Lewy Pathology in Living Parkinson\u2019s Disease Patients Undergoing Deep Brain Stimulation Findings challenge longstanding assumptions about how disease progresses and may redefine understanding of subtypes\u00a0<\/p>\n

New York, NY (July 1, 2026) Researchers at the Icahn School of Medicine at Mount Sinai have found that patients with Parkinson\u2019s disease undergoing deep brain stimulation (DBS) show\u00a0little to\u00a0no\u00a0Lewy pathology in the\u00a0prefrontal\u00a0cortex\u00a0at the time of\u00a0their DBS\u00a0surgery, despite\u00a0often having longstanding, clinically advanced disease.<\/p>\n

Published in\u00a0NPJ Parkinson\u2019s Disease\u00a0<\/a>[DOI: https:\/\/doi.org\/10.1038\/s41531-026-01422-8<\/a>], the findings provide important new insight into the relationship between\u00a0Parkinson\u2019s disease clinical symptoms and neuropathological\u00a0progression.\u00a0<\/p>\n

Lewy bodies are abnormal clumps\/aggregates\u00a0of the protein alpha-synuclein that build up inside nerve cells in the brain and are considered a pathological hallmark of Parkinson’s disease\u00a0and\u00a0are believed to accumulate throughout the brain as the disease progresses.\u00a0The absence of this pathology, particularly among patients presumed to be in later stages of disease progression, was\u00a0therefore unexpected.\u00a0Previous\u00a0studies\u2014largely in postmortem\u00a0tissue\u2014have\u00a0consistently found\u00a0widespread Lewy pathology in\u00a0patients\u00a0with advanced Parkinson\u2019s disease.\u00a0However, little\u00a0was\u00a0previously known about\u00a0how this hallmark of disease appears\u00a0in individuals, especially at the time of\u00a0DBS surgery.\u00a0<\/p>\n

As part of Mount Sinai\u2019s Living Brain Project<\/a>, researchers analyzed\u00a0prefrontal cortex samples taken\u00a0during\u00a0deep brain stimulation procedures\u00a0in\u00a0patients with\u00a0Parkinson\u2019s disease and in patients\u00a0undergoing DBS for other\u00a0neurologic conditions.\u00a0Researchers then compared the tissue samples to\u00a0determine\u00a0whether patients with Parkinson\u2019s disease had a greater burden of cortical Lewy pathology than the comparison group.\u00a0<\/p>\n

Unexpectedly,\u00a0nearly all\u00a0biopsies from patients with Parkinson\u2019s disease undergoing DBS\u00a0were negative for\u00a0Lewy bodies, and the overwhelming majority also lacked Lewy neurites, the abnormal nerve-cell proteins associated with Lewy\u00a0pathology. In contrast,\u00a0matched\u00a0postmortem samples from individuals with Parkinson\u2019s disease showed, as expected, a higher\u00a0burden of Lewy pathology\u00a0than control samples.\u00a0\u00a0<\/p>\n

\u201cWe were\u00a0surprised\u00a0to find that almost none of the patients living with\u00a0Parkinson\u2019s disease\u00a0had cortical Lewy bodies, particularly because many had been living with the disease for years,\u201d\u00a0said\u00a0Ariela\u00a0Buxbaum\u00a0Grice, a graduate student at the Icahn School of Medicine at Mount Sinai and lead author of the study.\u00a0\u201cBecause this\u00a0finding\u00a0was so unexpected, we carefully\u00a0evaluated\u00a0the\u00a0most likely\u00a0technical\u00a0explanations\u00a0and found that none could explain the near-absence of Lewy\u00a0bodies.\u00a0That\u00a0gives us confidence that\u00a0this reflects a\u00a0true\u00a0biological characteristic within this\u00a0patient\u00a0population, as opposed to a laboratory artifact.\u201d\u00a0\u00a0<\/p>\n

Noam\u00a0D. Beckmann,\u00a0PhD, Assistant Professor of Artificial Intelligence and Human Health at the Icahn School of Medicine at Mount Sinai and senior author of the study, said the findings underscore the importance of studying molecular pathology in the context of clinical characteristics.\u00a0\u00a0<\/p>\n

\u201cThis study demonstrates that clinical severity, disease progression, and neuropathological burden do not always advance together,\u201d Dr. Beckmann said. \u201cBy studying living brain tissue alongside detailed clinical data, we can begin to identify biologically meaningful subtypes of Parkinson\u2019s disease and better understand how the disease progresses, helping to guide more personalized treatment strategies in the future.\u201d\u00a0<\/p>\n

The study\u00a0also highlights\u00a0the\u00a0value of the\u00a0Living Brain\u00a0Project, a multiscale, data-driven research initiative that enables\u00a0researchers to study\u00a0living brain tissue collected during neurosurgical procedures. By integrating neuropathological analysis with detailed clinical information, investigators\u00a0can better understand disease biology as\u00a0it\u00a0develops in living patients, rather than relying solely on tissue collected after death.\u00a0\u00a0<\/p>\n

Brian Kopell, MD, Director of the Center for Neuromodulation, Co-Director of The Mount Sinai Hospital Movement Disorders Program, and Co-Lead of the Living Brain Project, emphasized the importance of studying living brain tissue in patients during advanced neurosurgical treatment.<\/p>\n

\u201cDeep brain stimulation offers a rare opportunity to study the biology of Parkinson\u2019s disease directly in living patients,\u201d Dr. Kopell said. \u201cMany of the patients had clinically significant motor\u00a0symptoms but\u00a0showed\u00a0very limited\u00a0cortical Lewy pathology. That disconnect could change how we think about disease progression and which patients may benefit most from deep brain stimulation.\u201d\u00a0<\/p>\n

Alexander Charney, MD, PhD, Director of The Charles Bronfman Institute for Personalized Medicine; Professor of Psychiatry, Neuroscience, and Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai; Co-Lead of the Living Brain Project;\u00a0and co-senior author on this manuscript, said the findings suggest that DBS candidates may represent a biologically distinct subgroup of Parkinson\u2019s disease patients.<\/p>\n

\u201cThese findings challenge the assumption that patients undergoing deep brain stimulation necessarily have widespread cortical Lewy pathology based solely on disease duration or symptom severity,\u201d Dr. Charney said. \u201cInstead, our findings suggest that many DBS patients may represent a motor-predominant subtype of Parkinson\u2019s disease with relatively limited cortical involvement.\u201d\u00a0<\/p>\n

The findings suggest that Parkinson\u2019s disease may progress differently across biologically distinct patient groups, highlighting the complexity of the disease and the need for additional research. Rather than reflecting uniformly advanced neuropathology, patients selected for deep brain stimulation may\u00a0represent\u00a0a subgroup with slower or regionally distinct patterns of Lewy body accumulation.\u00a0<\/p>\n

Additional\u00a0longitudinal and\u00a0postmortem studies will be needed to\u00a0determine\u00a0whether DBS patients experience slower cortical disease\u00a0progression or represent a distinct biological subtype of Parkinson\u2019s disease.<\/p>\n

This work was supported by the National Institute on Aging and the Michael J. Fox Foundation.<\/p>\n

About the Icahn School of Medicine at Mount Sinai
The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the seven member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to New York City\u2019s large and diverse patient population.\u00a0<\/p>\n

The Icahn School of Medicine at Mount Sinai offers highly competitive MD, PhD, MD-PhD, and master\u2019s degree programs, with enrollment of more than 1,200 students. It has the largest graduate medical education program in the country, with more than 2,700 clinical residents and fellows training throughout the Health System. The Graduate School of Biomedical Sciences offers 12 degree-granting programs, conducts innovative basic and translational research, and trains more than 470 postdoctoral research fellows.<\/p>\n

Ranked 11th nationwide in National Institutes of Health (NIH) funding, the Icahn School of Medicine at Mount Sinai is among the 90th percentile of U.S. private medical schools in Sponsored Programs Direct Expenditures per Principal Investigator, according to the Association of American Medical Colleges.\u00a0 More than 6,900 scientists, educators, and clinicians work within and across dozens of academic departments and multidisciplinary institutes with an emphasis on translational research and therapeutics. Through Mount Sinai Innovation Partners (MSIP), the Health System facilitates the real-world application and commercialization of medical breakthroughs made at Mount Sinai.<\/p>\n

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* Mount Sinai Health System member hospitals: The Mount Sinai Hospital; Mount Sinai Brooklyn; Mount Sinai Morningside; Mount Sinai Queens; Mount Sinai South Nassau; Mount Sinai West; and New York Eye and Ear Infirmary of Mount Sinai. \u00a0<\/p>\n

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