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Cerebrospinal fluid biomarkers and clinical features in leucine‐rich repeat kinase 2 ( LRRK2 ) mutation carriers
Author(s) -
Vilas Dolores,
Shaw Leslie M.,
Taylor Peggy,
Berg Daniela,
Brockmann Kathrin,
Aasly Jan,
Marras Connie,
PontSunyer Claustre,
Ríos José,
Marek Ken,
Tolosa Eduardo
Publication year - 2016
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.26591
Subject(s) - lrrk2 , cerebrospinal fluid , parkinson's disease , medicine , alpha synuclein , pathophysiology , pathology , disease
Background Mutations in the leucine‐rich repeat kinase 2 ( LRRK2 ) gene are the most common cause of inherited Parkinson's disease (PD). Nonmanifesting carriers of LRRK2 mutations are at high risk for developing PD. Information available on cerebrospinal fluid (CSF) biomarkers in LRRK2 carriers remains preliminary. Objectives To measure CSF levels of α‐synuclein, β amyloid 1‐42 , total‐tau, and phospho‐tau 181 , in LRRK2‐ associated PD, idiopathic PD, nonmanifesting carriers, and first‐degree relatives of LRRK2‐ associated PD patients without the mutation (nonmanifesting noncarriers). To correlate the clinical features and the integrity of the nigrostriatal pathway assessed by neuroimaging with the CSF biomarkers. Methods 138 CSF samples provided by the Michael J. Fox Foundation LRRK2 Cohort Consortium were analyzed: 28 LRRK2‐ associated PD, 35 idiopathic PD, 41 nonmanifesting carriers, and 34 nonmanifesting noncarriers. All of the participants in the study were clinically assessed. Most of the participants underwent a dopamine transporter scan to assess the integrity of the nigrostriatal pathway. Results CSF levels of α‐synuclein were similar in LRRK2‐ associated PD, nonmanifesting carriers, and nonmanifesting noncarriers but significantly higher than in idiopathic PD ( P = .041). No differences were found in the concentrations of β amyloid 1‐42 , total‐tau, or phospho‐tau 181 among study groups. CSF alpha‐synuclein levels strongly correlated with total‐tau and phospo‐tau 181 levels in all groups. No significant correlation was found between the CSF biomarkers and the striatal binding ratios for (123)I‐FP‐CIT in nonmanifesting carriers. Conclusion The CSF protein profile differs in LRRK2‐ associated PD and idiopathic PD, suggesting that pathophysiological mechanisms different from IPD underlie LRRK2‐ associated PD. Cerebrospinal fluid biomarkers did not prove helpful in differentiating asymptomatic LRRK2 mutation carriers from noncarriers. © 2016 International Parkinson and Movement Disorder Society