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Lewy bodies are usually accompanied by Alzheimer disease-related changes, cerebrovascular lesions, and TDP-43 pathology, alongside diverse combinations including cardiovascular disorders, metabolic syndrome, diabetes, autoimmune and rheumatic diseases, and other rarer conditions. The article discusses immune-related links between PD and multiple sclerosis, and the impacts of COVID-19 and HIV. Epidemiological patterns suggest altered cancer risk, and the observed heterogeneity likely reflects complex interactions among genetic, pathogenic, and other risk factors, motivating further research for better diagnostics and disease-modifying therapies.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/concomitant-pathologies-and-their-impact-on-parkinson-disease-a-narrative-overview-of-current-evidence/369377/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/concomitant-pathologies-and-their-impact-on-parkinson-disease-a-narrative-overview-of-current-evidence/369377.png","ImageObject",300,407,{"name":92,"@type":93},"Mia  ","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What major co-pathologies commonly co-occur with Parkinson disease?","Question",{"text":112,"@type":113},"Lewy body pathology in PD rarely appears alone and is typically associated with Alzheimer disease-related changes, cerebrovascular pathologies, and TDP-43 pathology, often in multiple combinations.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How can co-pathologies affect PD progression and cognitive impairment?",{"text":117,"@type":113},"Some co-pathologies, including microinfarcts, atherosclerosis, arteriolosclerosis, cerebral amyloid angiopathy, and tau pathology, are linked to disease progression and cognitive impairment, while others may not contribute in the same way.",{"name":119,"@type":110,"acceptedAnswer":120},"What does the review suggest about why co-pathologies are so heterogeneous across PD patients?",{"text":121,"@type":113},"The review attributes the wide heterogeneity to complex interplay among genetic factors, pathogenic mechanisms, and other risk factors, and emphasizes the need for further research to clarify relationships with idiopathic PD and guide improved diagnostics and therapies.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},369377,1790752018,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},687207024478,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Review  \nConcomitant Pathologies and Their Impact on Parkinson Disease: A Narrative Overview of Current Evidence  \nKurt A. Jellinger   \nAcademic Editor: Maria Anttonietta Panaro  \nReceived: 26 February 2025  \nRevised: 19 March 2025  \nAccepted: 20 March 2025  \nPublished: 24 March 2025  \nCitation: Jellinger, K.A. Concomitant Pathologies and Their Impact on Parkinson Disease: A Narrative Overview of Current Evidence. Int. J. Mol. Sci. 2025, 26, 2942. [https://](https://)[ ](https://)[doi.org/10.3390/ijms26072942](doi.org/10.3390/ijms26072942)  \n[Copyright:](Copyright:) © 2025 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \nInstitute of Clinical Neurobiology, Alberichgasse 5/13, A-1150 Vienna, Austria; [kurt.jellinger@univie.ac.at](kurt.jellinger@univie.ac.at); Tel./Fax: +43-1-5266534  \nAbstract: Many clinico-pathological studies point to the presence of multiple comorbidities/ co-pathologies in the course of Parkinson disease (PD) . Lewy body pathology, the morphological hallmark of PD, rarely exists in isolation, but is usually associated with other concomitant pathologies, in particular Alzheimer disease-related changes (ADNC), cerebrovascular pathologies (macro-and microinfarcts, cerebral small vessel disease, cerebral amyloidangiopathy), TDP-43 pathology as well as multiple pathological combinations. These include cardiovascular disorders, metabolic syndrome, diabetes mellitus, autoimmune and rheumatic diseases, myasthenia gravis, Sjögren’s syndrome, restless leg syndrome or other rare disorders, like Fabry disease. A combination of PD and multiple sclerosis (MS) may be due to the immune function of LRRK2 and its interrelation with α-synuclein. COVID-19 and HIV posed considerable impacts on patients with PD. Epidemiological evidence points to a decreased risk for the majority of neoplasms, except melanoma and other skin cancers, while some tumors (breast, brain) are increased. On the other hand, a lower frequency of malignancies preceding early PD markers may argue for their protective effect on PD risk. Possible pathogenetic factors for the association between PD and cancer are discussed. The tremendous heterogeneity of concomitant pathologies and comorbidities observed across the PD spectrum is most likely caused by the complex interplay between genetic, pathogenic and other risk factors, and further research should provide increasing insight into their relationship with idiopathic PD (and other parkinsonian disorders) in order to find better diagnostic tools and probable disease-modifying therapies.  \nKeywords: Parkinson disease; co-pathologies; comorbidities; Alzheimer lesions; cerebrovascular; autoimmune diseases; diabetes mellitus; myasthenia gravis; COVID-19  \n1. Introduction  \nParkinson disease (PD), the second most common neurodegenerative disorder, isneuropathologically characterized by the widespread intraneuronal and neuritic deposition of abnormal phosphorylated α-synuclein-forming Lewy bodies (LBs) and Lewy neurites, the morphological hallmarks of PD and related LB disorders. They induce progressive degeneration not only of the dopaminergic nigrostriatal system, but of many other neuronal and extraneural systems; PD is thus a multisystem disorder. The site of origin of α-synuclein (αSyn) deposition is a matter of ongoing discussion, since it was suggested either to originate in the olfactory bulb and to progress upward to interconnected brain regions [1,2], or in the enteric system, propagating to the brainstem with caudo-rostral progression throughout the brain [3] . Similarly to other neurodegenerative disorders, brain co-pathologies have increasingly been recognized as a rule (>90%) and not an exception in PD, with PD patients exhibiting a mi","cbCaip53tpLwtr0I","https://ap.wps.com/l/cbCaip53tpLwtr0I","pdf",783769,32,"English","# Introduction\n## Parkinson disease pathology and multisystem involvement\n## Brain co-pathologies and their clinical influence\n## Non-AD neurodegenerative co-pathologies and combinations","[{\"question\":\"What major co-pathologies commonly co-occur with Parkinson disease?\",\"answer\":\"Lewy body pathology in PD rarely appears alone and is typically associated with Alzheimer disease-related changes, cerebrovascular pathologies, and TDP-43 pathology, often in multiple combinations.\"},{\"question\":\"How can co-pathologies affect PD progression and cognitive impairment?\",\"answer\":\"Some co-pathologies, including microinfarcts, atherosclerosis, arteriolosclerosis, cerebral amyloid angiopathy, and tau pathology, are linked to disease progression and cognitive impairment, while others may not contribute in the same way.\"},{\"question\":\"What does the review suggest about why co-pathologies are so heterogeneous across PD patients?\",\"answer\":\"The review attributes the wide heterogeneity to complex interplay among genetic factors, pathogenic mechanisms, and other risk factors, and emphasizes the need for further research to clarify relationships with idiopathic PD and guide improved diagnostics and therapies.\"}]","Concomitant Pathologies and Their Impact on Parkinson Disease - A Narrative Overview of Current Evidence | PDF",1790182300,81]