title: Correlation between decreased CSF α-synuclein and Aβ₁₋₄₂ in Parkinson disease.
abstract: Accumulation of misfolded α-synuclein (α-syn) protein in Lewy bodies and neurites is the cardinal pathologic feature of Parkinson disease (PD), but abnormal deposition of other proteins may also play a role. Cerebrospinal fluid (CSF) levels of proteins known to accumulate in PD may provide insight into disease-associated changes in protein metabolism and their relationship to disease progression. We measured CSF α-syn, amyloid β₁₋₄₂ (Aβ₁₋₄₂), and tau from 77 nondemented PD and 30 control participants. CSF α-syn and Aβ₁₋₄₂ were significantly lower in PD compared with controls. In contrast with increased CSF tau in Alzheimer disease, CSF tau did not significantly differ between PD and controls. CSF protein levels did not significantly correlate with ratings of motor function or performance on neuropsychological testing. As expected, CSF Aβ₁₋₄₂ inversely correlated with [(11)C]-Pittsburgh compound B (PiB) mean cortical binding potential, with PiB(+) PD participants having lower CSF Aβ₁₋₄₂ compared with PiB(-) PD participants. Furthermore, CSF α-syn positively correlated with Aβ₁₋₄₂ in PD participants but not in controls, suggesting a pathophysiologic connection between the metabolisms of these proteins in PD.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St Louis, MO, USA; Department of Developmental Biology, Washington University School of Medicine, St Louis, MO, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Chandana
authors.initials: C
authors.lastname: Buddhala
authors.affiliation: Department of Neurology, Washington University School of Medicine, St Louis, MO, USA; Department of Radiology, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Meghan C
authors.initials: MC
authors.lastname: Campbell
authors.affiliation: Department of Neurology, Washington University School of Medicine, St Louis, MO, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO, USA; Department of Radiology, Washington University School of Medicine, St Louis, MO, USA; Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO, USA; Program in Occupational Therapy, Washington University School of Medicine, St Louis, MO, USA; Program in Physical Therapy, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Perlmutter
authors.affiliation: Department of Neurology, Washington University School of Medicine, St Louis, MO, USA; Department of Developmental Biology, Washington University School of Medicine, St Louis, MO, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO, USA. Electronic address: kotzbauerp@wustl.edu.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Kotzbauer
mesh_terms: D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid* / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D003071:Cognition; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D010446:Peptide Fragments / Q000134:cerebrospinal fluid* / Q000378:metabolism; D011597:Psychomotor Performance; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid* / Q000378:metabolism; D016875:tau Proteins / Q000134:cerebrospinal fluid / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D010446:Peptide Fragments; D051844:alpha-Synuclein; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Aβ(1–42); Cerebrospinal fluid; Imaging; Nondemented; Parkinson’s disease; PiB; Tau; α-Synuclein