From disease to syndrome: the evolution of Parkinson's as a heterogeneous entity.
From disease to syndrome: the evolution of Parkinson's as a heterogeneous entity.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Sydney, AU · Author affiliation
Molecular Medicine Laboratory and Department of Neurology, Concord Repatriation General Hospital, Concord, NSW 2139, Australia; Concord Clinical School, University of Sydney, Concord, NSW 2139, Australia; Genomics and Inherited Disease Program, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; School of Clinical Medicine, UNSW Medicine & Health, University of New South Wales, Kensington, NSW 2033, Australia. Electronic address: kkum4618@uni.sydney.edu.au.Location evidence
GB · Author affiliation · country only
Molecular Medicine Laboratory and Department of Neurology, Concord Repatriation General Hospital, Concord, NSW 2139, Australia; Concord Clinical School, University of Sydney, Concord, NSW 2139, Australia; Genomics and Inherited Disease Program, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; School of Clinical Medicine, UNSW Medicine & Health, University of New South Wales, Kensington, NSW 2033, Australia. Electronic address: kkum4618@uni.sydney.edu.au.Location evidence
AU · Author affiliation · country only
Department of Neurology, St. Vincent's Hospital, Darlinghurst, NSW 2010, Australia; Discipline of Medicine, St Vincent's Healthcare Clinical Campus, University of New South Wales, Darlinghurst, NSW 2010, Australia.Location evidence
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Original abstract
Parkinson's disease (PD) is increasingly recognised as a multifactorial and heterogeneous condition rather than a single uniform disorder, supported by advances in molecular biology, genetics and pathology. This review provides a perspective on the shifting concept of PD from an idiopathic, strictly defined pathological entity to a highly heterogeneous clinical and etiopathological condition. We outline the diverse aetiologic pathways and clinical expressions of PD, with particular emphasis on genetic contributors and the role of neuroinflammation. Genetic studies have identified monogenic causes - including SNCA, LRRK2, VPS35, RAB32, PRKN and PINK1 - as well as increased risk linked to heterozygous GBA1variants and more than 90 susceptibility loci from genome-wide association studies (GWAS), highlighting converging pathogenic mechanisms. Recent work underscores significant involvement of innate and adaptive immune responses from the earliest disease stages, suggesting a central shared role in PD onset and progression. This contemporary framework opens new avenues for biology-based, disease-modifying therapeutic strategies.