α-Synuclein Conformations in Plasma Distinguish Parkinson's Disease from Dementia with Lewy Bodies.

Autor:	Kannarkat GT; Department of Neurology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA, USA, 19104., Zack R; Department of Neurology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA, USA, 19104., Skrinak RT; Department of Neurology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA, USA, 19104., Morley JF; Department of Neurology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA, USA, 19104.; Parkinson's Disease Research, Education and Clinical Center, Corporal Michael J. Crescenz VA Medical Center; Philadelphia, PA, USA, 19104., Davila-Rivera R; Department of Neurology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA, USA, 19104., Arezoumandan S; Department of Neurology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA, USA, 19104., Dorfmann K; Department of Neurology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA, USA, 19104., Luk K; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA, USA, 19104., Wolk DA; Department of Neurology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA, USA, 19104., Weintraub D; Parkinson's Disease Research, Education and Clinical Center, Corporal Michael J. Crescenz VA Medical Center; Philadelphia, PA, USA, 19104.; Department of Psychiatry and Neurology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA, USA, 19104., Tropea TF; Department of Neurology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA, USA, 19104., Lee EB; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA, USA, 19104., Xie SX; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA, USA, 19104., Chandrasekaran G; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA, USA, 19104., Lee VM; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA, USA, 19104., Irwin D; Department of Neurology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA, USA, 19104., Akhtar RS; Ken and Ruth Davee Department of Neurology and Simpson Querrey Center for Neurogenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA, 60611., Chen-Plotkin AS; Department of Neurology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA, USA, 19104.
Jazyk:	angličtina
Zdroj:	Research square [Res Sq] 2024 Sep 17. Date of Electronic Publication: 2024 Sep 17.
DOI:	10.21203/rs.3.rs-5033901/v1
Abstrakt:	Aggregation of misfolded α-synuclein (aSyn) within the brain is the pathologic hallmark of Lewy body diseases (LBD), including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Evidence exists for aSyn "strains" - conformations with distinct biological properties. However, biomarkers for PD vs. DLB, including potential aSyn strain differences, are lacking. Here, we used two monoclonal antibodies selective for different in vitro aSyn species - termed Strain A and B - to evaluate human brain tissue, cerebrospinal fluid (CSF), and plasma. Surprisingly, levels of Strain A and B aSyn species differed in plasma from individuals with PD vs. DLB in two independent cohorts. Lower plasma aSyn Strain A species also predicted subsequent PD cognitive decline. Strain A and Strain B aSyn species were undetectable in CSF, but plasma aSyn species could template aSyn fibrillization, particularly in PD. Our findings suggest that aSyn strains may impact LBD clinical presentation and originate outside the brain. Competing Interests: Competing interests: Dr Tropea has received consulting fees and honoraria from Sanofi Genzyme, Bial, and the Parkinson Foundation. The following authors declare that they have no competing interests: GTK, SA, RSA JFM, ACP, DJI, RTS, RDR, KD, VL.
Databáze:	MEDLINE
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