title: Αlpha-synuclein levels in blood plasma from LRRK2 mutation carriers.
abstract: The diagnosis of Parkinson's disease (PD) remains primarily a clinical issue, based mainly on phenotypic patterns. The identification of biomarkers capable of permitting the preclinical detection of PD is critically needed. α-Synuclein is a key protein in PD, with missense and multiplication mutations in the gene encoding α-synuclein (SNCA) having been reported in familial cases of PD, and accumulation of the protein identified in Lewy bodies (LBs) and Lewy neurites (LNs) in affected brain regions. With the objective of validating the use of α-synuclein as a clinical or progressive biomarker in an accessible tissue, we used an enzyme-linked immunosorbent assay (ELISA) to measure α-synuclein levels in the peripheral blood plasma of idiopathic PD and LRRK2 mutation carrier patients and compared our findings with healthy control subjects. Compared to healthy controls, we found a significant decrease in plasma total α-synuclein levels in idiopathic PD (iPD) patients (n = 134, p = 0.010). However, the reduction was less significant in patients who were LRRK2 mutation carriers (n = 32, p = 0.133). This lack of significance could be due to the small number of individuals employed in this group. No predictive value of total α-synuclein in the diagnosis of PD was found in a receiver operating characteristic (ROC) curve analysis. Although this is a pilot study requiring corroboration on a larger cohort of patients, our results highlight the possible use of plasma α-synuclein as a biomarker for PD.
authors.affiliation: Biodonostia Research Institute, Neurosciences area, Donostia, Gipuzkoa, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Gorostidi
authors.forename: Alberto
authors.initials: A
authors.lastname: Bergareche
authors.forename: Javier
authors.initials: J
authors.lastname: Ruiz-Martínez
authors.forename: José F
authors.initials: JF
authors.lastname: Martí-Massó
authors.forename: María
authors.initials: M
authors.lastname: Cruz
authors.forename: Shiji
authors.initials: S
authors.lastname: Varghese
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Qureshi
authors.forename: Fatimah
authors.initials: F
authors.lastname: Alzahmi
authors.forename: Abdulmonem
authors.initials: A
authors.lastname: Al-Hayani
authors.forename: Adolfo
authors.initials: A
authors.lastname: López de Munáin
authors.forename: Omar M A
authors.initials: OM
authors.lastname: El-Agnaf
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D009154:Mutation; D010300:Parkinson Disease / Q000097:blood / Q000235:genetics; D055503:Protein Multimerization; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D020836:Protein Structure, Quaternary; D051844:alpha-Synuclein / Q000097:blood* / Q000737:chemistry
chemical_list: D051844:alpha-Synuclein; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases