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Cited by 150Lysosomal Storage Disorders ResearchParkinson's Disease Mechanisms and TreatmentsGlycogen Storage Diseases and Myoclonus

Clinical and Biochemical Differences in Patients Having Parkinson Disease With vs Without GBA Mutations

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Chahine, Lama M., Qiang, Judy, Ashbridge, Emily, Minger, James, Yearout, Dora, Horn, Stacy, Colcher, Amy, Hurtig, Howard I. +7 more·2013·JAMA Neurology
DOI 10.1001/jamaneurol.2013.1274PMC PMC3762458
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Abstract

IMPORTANCE: Biochemical abnormalities present in GBA (mut/wt) carriers may offer new pathogenetic insights to and potential therapeutic targets in Parkinson disease (PD). OBJECTIVE: To determine whether patients having PD with vs without GBA mutations differ in clinical phenotype or plasma protein expression. DESIGN AND SETTING: Case-control study of patients having PD with vs without GBA mutations. Clinical characteristics were compared between groups, and biochemical profiling of 40 plasma proteins was performed to identify proteins that differed in expression between groups. PARTICIPANTS: The discovery cohort included 20 patients having PD with GBA mutations. Clinical characteristics of GBA-associated PD cases were compared with those of 242 patients having PD in whom GBA mutations were excluded by full gene sequencing. MAIN OUTCOME MEASURES: Biochemical profiling was available for all 20 GBA-associated PD cases, as well as a subset (87 of 242) of the GBA-negative PD cases. The replication cohort included 19 patients having PD with GBA mutations and 41 patients having PD without GBA mutations. RESULTS: Compared with patients having PD without GBA mutations, patients having PD with GBA mutations were younger at disease onset (P = .04) and were more likely to demonstrate cognitive dysfunction (P = .001). In a multiple regression model that included age, sex, and assay batch as covariates, GBA mutation status was significantly associated with plasma levels of interleukin 8 (P = .001), monocyte chemotactic protein 1 (P = .008), and macrophage inflammatory protein 1α (P = .005). The association between interleukin 8 and GBA mutation status was replicated (P = .03) in a separate cohort of patients having PD with vs without GBA mutations. CONCLUSIONS AND RELEVANCE: Patients having PD with GBA mutations have earlier age at disease onset and are more likely to demonstrate cognitive dysfunction. Monocyte-associated inflammatory mediators may be elevated in patients having PD with GBA mutations.

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  • PD patients with GBA mutation have increased plasma levels of chemokines, including CCL2, CXCL8, and CCL3.

    “In line with this, PD patients with GBA mutation have increased plasma levels of chemokines, including CCL2, CXCL8, and CCL3.264”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [264]

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Authors
Chahine, L. M., Qiang, J., Ashbridge, E., Minger, J., Yearout, D., Horn, S., Colcher, A., Hurtig, H. I., Lee, V. M.-Y., Van Deerlin, V. M., Leverenz, J. B., Siderowf, A. D., Trojanowski, J. Q., Zabetian, C. P., & Chen-Plotkin, A.
Affiliations
  • University of Pennsylvania (US)
  • University of Washington (US)
ORCID
Venue
JAMA Neurology
Publisher
American Medical Association (AMA)
Published
2013-07-01
Volume
70
Issue
7
Pages
852
ISSN
2168-6149 (ISSN-L)
DOI
10.1001/jamaneurol.2013.1274
PMC
PMC3762458
OpenAlex
W2043492026
Cited by
150
References
0
Citations by year
2026: 15 · 2025: 5 · 2024: 7 · 2023: 12 · 2022: 27 · 2021: 15 · 2020: 10 · 2019: 3 · 2018: 9 · 2017: 12 · 2016: 9 · 2015: 14 · 2014: 11 · 2013: 1
FWCI
8.12
Type
journal article
Language
en
Open access
Locations
  • JAMA Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Veterans Affairs (I01 BX000531)
  • National Institute on Aging (AG033101, K08AG033101)
  • National Institute of Neurological Disorders and Stroke (NS053488, P50NS062684, R01NS065070, P50NS053488, U01NS082134)
Topics
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
Keywords
Parkinson's disease, GBA mutations, glucocerebrosidase, plasma protein expression, interleukin-8, MCP-1, macrophage inflammatory protein-1alpha, cognitive impairment, age of onset, neuroinflammation, clinical phenotype
MeSH terms
Age Factors, Aged, beta-Glucosidase, Blood Proteins, Female, Genotype, Humans, Male, Middle Aged, Mutation, Parkinson Disease, Phenotype, Cohort Studies, Case-Control Studies, Age of Onset, Genetic Predisposition to Disease

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