title: Lower plasma apolipoprotein A1 levels are found in Parkinson's disease and associate with apolipoprotein A1 genotype.
abstract: The discovery of novel plasma-based biomarkers could lead to new approaches in the treatment of Parkinson's disease (PD). Here, we explore the role of plasma apolipoprotein A1 (ApoA1) as a risk marker for PD and evaluate the influence of APOA1 promoter variation on plasma ApoA1 levels. Plasma ApoA1 and the single-nucleotide polymorphism, rs670, were assayed in a discovery cohort (cohort 1) of 301 PD patients, 80 normal controls (NCs), and 165 subjects with other neurodegenerative diseases, as well as a cohort (cohort 2) of 158 PD patients from a second clinical site. Additionally, rs670 was genotyped in a third cohort of 1,494 PD and 925 NC subjects from both clinical sites. Compared to both normal and disease controls, PD patients have lower plasma ApoA1 (P < 0.001 for both comparisons). Moreover, in PD patients, plasma ApoA1 levels are correlated with genotype at the APOA1 promoter polymorphism, rs670. Specifically, lower plasma ApoA1 levels were found in rs670 major allele (G) homozygotes in both cohort 1 (P = 0.009) and in a replication cohort (cohort 2; n = 158 PD patients; P = 0.024). Finally, evaluating rs670 genotype frequencies in 1,930 PD cases versus 997 NCs, the rs670 GG genotype shows a trend toward association (odds ratio: 1.1; P = 0.10) with PD. Our results are compatible with a model whereby circulating ApoA1 levels may be useful in risk-stratifying subjects for the development of PD, with higher ApoA1 levels suggesting relative protection. Future studies evaluating modulation of ApoA1 as a novel therapeutic strategy in PD are warranted. © 2014 International Parkinson and Movement Disorder Society.
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Christine R
authors.initials: CR
authors.lastname: Swanson
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Travis L
authors.initials: TL
authors.lastname: Unger
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Cellular and Molecular Biology Graduate Group, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Gallagher
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Vivianna M
authors.initials: VM
authors.lastname: Van Deerlin
authors.affiliation: Booth Gardner Parkinson's Care Center, Evergreen Hospital Medical Center, Kirkland, Washington, USA.
authors.forename: Pinky
authors.initials: P
authors.lastname: Agarwal
authors.affiliation: Cleveland Clinic Ruvo Center for Brain Health, Cleveland, Ohio, USA.
authors.forename: James
authors.initials: J
authors.lastname: Leverenz
authors.affiliation: Virginia Mason Medical Center, Seattle, Washington, USA.
authors.forename: John
authors.initials: J
authors.lastname: Roberts
authors.affiliation: VA Puget Sound Health Care System and Department of Neurology, University of Washington Seattle, Seattle, Washington, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Samii
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Rachel Goldmann
authors.initials: RG
authors.lastname: Gross
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Hurtig
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Rick
authors.affiliation: Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Weintraub
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.affiliation: VA Puget Sound Health Care System and Department of Neurology, University of Washington Seattle, Seattle, Washington, USA.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Zabetian
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Alice S
authors.initials: AS
authors.lastname: Chen-Plotkin
mesh_terms: D000368:Aged; D000483:Alleles; D016632:Apolipoprotein A-I / Q000097:blood* / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010300:Parkinson Disease / Q000097:blood* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D015415:Biomarkers
keywords: ApoA1; Apolipoprotein A1; Parkinson's disease; biomarker; genotype