Adler CH

Berg D

Hoglinger GU

Klein C

Lang AE

Outeiro TF

Poewe W

Postuma R

Stoessl AJ

English

Newcastle University E-Prints

Received: 19 September 2024 Accepted: 4 November 2024DOI: 10.1002/alz.14449L E T T E RInitial biological classification of Lewy body diseases: Noconsensus on terminologyTo the Editor,We readwith considerable interest the revised criteria for the diag-nosis and staging of Alzheimer’s disease (AD) by Jack et al.1 Thissummarizes the long history and multi-staged development and evo-lution of biological concepts underlying their updated proposal. Giventhe frequency of Lewy body co-pathology in AD, we agree with theinclusion of alpha synuclein as a biomarker for non-AD co-pathologyin AD, especially given its potential impact on the clinical course (e.g.,Levin et al.2). Conversely, we also propose to consider amyloid beta andtau as potential co-pathology whichmay be of relevance in biologicallydefined Parkinson’s disease (PD).3 However, when discussing biomark-ers for alpha synuclein,1 the authors state that PD and dementia withLewy bodies (DLB) “have recently been re-labeled asNSD” (NSD: “neu-ronal synuclein disease”), and this is repeated throughout the article.We wish to highlight that the term “NSD” is not currently an accepteddesignation by the PD or DLB communities. This terminology and con-cept have not been carefully evaluated in thewayADproposed criteriahave. The term NSD and its accompanying integrated staging systemhave only recently been proposed in a single article,4 and have notbeen sufficiently considered, vetted, and supported by large segmentsof the research community dealing with alpha synuclein–related dis-eases (the community at large currently rather uses the term “Lewybody disorder” or “Lewy body disease” as the umbrella term for PDand DLB5,6 and we have also argued that the diagnosis of PD shouldnot be restricted to those with Lewy pathology).3 Indeed, this proposalhas engendered considerable discussion and controversy in the field,and disagreement has already been registered from researchers in theareas of rapid eye movement behavior disorder,7 dementia with Lewybodies8 and neuropathology,9 as well as the International ParkinsonandMovement Disorder Society.10 We are at the earliest stages in thedevelopment of a biological classification/definition of Lewy body dis-eases, and, until the field can reach greater consensus, we considerthat it would be unwise to portray, accept, or endorse the re-labelingof PD and DLB as NSD by the AD community. This is particularly rele-vant given theproposal for including alpha synuclein seedamplificationassays as a biomarker for non-AD co-pathology.ACKNOWLEDGMENTSThe authors have nothing to report.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, providedthe original work is properly cited.© 2024 The Author(s). Alzheimer’s & Dementia published byWiley Periodicals LLC on behalf of Alzheimer’s Association.CONFLICT OF INTEREST STATEMENTThe authors declare no conflicts of interest. Author disclosures areavailable in the supporting information.FUNDING INFORMATIONNothing relevant to this letter.Anthony E. Lang1Günter U. Höglinger2,3,4Charles H. Adler5Daniela Berg6Christine Klein7Tiago FlemingOuteiro8,9Werner Poewe10Ron Postuma11A. Jon Stoessl121Edmond J. Safra Program in Parkinson’s Disease and the Rossy PSPCentre, TorontoWestern Hospital and the University of Toronto, Toronto,Ontario, Canada2Department of Neurology, LMUUniversity Hospital,Ludwig-Maximilians-Universität (LMU), Munich, Germany3German Center for Neurodegenerative Diseases (DZNE), Munich,Germany4Munich Cluster for Systems Neurology (SyNergy), Munich, Germany5Mayo Clinic Alix School of Medicine, Mayo Clinic Arizona, Scottsdale,Arizona, USA6Christian-Albrechts-University and University HospitalSchleswig-Holstein, Campus Kiel, Kiel, Germany7Schilling Professor of Neurogenetics and Neurology, Director of theInstitute of Neurogenetics, University of Luebeck and University HospitalSchleswig-Holstein, Lüebeck, Germany8University Medical Center Göttingen, Department of ExperimentalNeurodegeneration, Center for Biostructural Imaging ofNeurodegeneration, Göttingen, Germany9Translational and Clinical Research Institute, Faculty of Medical Sciences,Newcastle University, Newcastle Upon Tyne, UK10Medical University Innsbruck, Innsbruck, AustriaAlzheimer’s Dement. 2024;1–2. wileyonlinelibrary.com/journal/alz 12 LETTER11Department of Neurology and Neurosurgery, The Neuro (MontrealNeurological Institute-Hospital), McGill University, Montreal, Quebec,Canada12DjavadMowafaghian Centre for Brain Health, Faculty of Medicine,University of British Columbia, Vancouver, British Columbia, CanadaCorrespondenceAnthony E. Lang, Edmond J. Safra Program in Parkinson’s Disease andthe Rossy PSP Centre, TorontoWestern Hospital and the University ofToronto, 399 Bathurst St., 7MC-412, TorontoONM5T 2S8, Canada.Email: anthony.lang@uhn.caORCIDAnthonyE. Lang https://orcid.org/0000-0003-1229-3667REFERENCES1. Jack CR Jr, Andrews JS, Beach TG, et al. Revised criteria for diag-nosis and staging of Alzheimer’s disease: alzheimer’s AssociationWorkgroup. Alzheimers Dement. 2024;20(8):5143-5169.2. Levin J, Baiardi S, Quadalti C, et al. alpha-Synuclein seed amplifica-tion assay detects Lewy body co-pathology in autosomal dominantAlzheimer’s disease late in the disease course and dependent on Lewypathology burden. Alzheimers Dement. 2024;20:4351-4365.3. Hoglinger GU, Adler CH, Berg D, et al. A biological classificationof Parkinson’s disease: the SynNeurGe research diagnostic criteria.Lancet Neurol. 2024;23:191-204.4. Simuni T, Chahine LM, Poston K, et al. A biological definition of neu-ronal alpha-synuclein disease: towards an integrated staging systemfor research. Lancet Neurol. 2024;23:178-190.5. LippaCF,Duda JE, GrossmanM, et al. DLB andPDDboundary issues—Diagnosis, treatment,molecular pathology, and biomarkers.Neurology.2007;68:812-819.6. Irwin DJ, Grossman M, Weintraub D, et al. Neuropathologicaland genetic correlates of survival and dementia onset in synu-cleinopathies: a retrospective analysis. Lancet Neurol. 2017;16:55-65.7. Boeve BF, Davis AA, Ju YE, Kantarci K, Singer W, Videnovic A. Con-cerns with the new biological research criteria for synucleinopathy.Lancet Neurol. 2024;23:659-660.8. Goldman JG, Boeve BF, Galasko D, Galvin JE, Leverenz JB, Taylor JP.Concerns with the new biological research criteria for synucleinopa-thy. Lancet Neurol. 2024;23:660-661.9. Kovacs GG, Grinberg LT, Halliday G, et al. Biomarker-based approachto alpha-Synucleinopathies: lessons from neuropathology.Mov Disord.2024. in press.10. Kalia LV, Berg D, Kordower JH, et al. Movement disorders societyviewpoint on biological frameworks of Parkinson’s disease: currentstatus and future directions.Mov Disord. 2024;39(10):1710-1715.SUPPORTING INFORMATIONAdditional supporting information can be found online in the Support-ing Information section at the end of this article. 15525279, 0, Downloaded from https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.14449 by NEWCASTLE UNIVERSITY, Wiley Online Library on [13/01/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

Initial biological classification of Lewy body diseases: No consensus on terminology

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Initial biological classification of Lewy body diseases: No consensus on terminology

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