Cerebrospinal fluid biomarkers of central catecholamine deficiency in Parkinson's disease and other synucleinopathies

• Published in: Brain (London, England : 1878) England : 1878), 2012-06, Vol.135 (Pt 6), p.1900-1913
• Main Authors: GOLDSTEIN, David S, HOLMES, Courtney, SHARABI, Yehonatan
• Format: Article
• Language: English
• Subjects: 3,4-Dihydroxyphenylacetic Acid - cerebrospinal fluid; Aged; Biological and medical sciences; Biomarkers - blood; Biomarkers - cerebrospinal fluid; Catecholamines - blood; Catecholamines - cerebrospinal fluid; Catecholamines - deficiency; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dopamine Agents - therapeutic use; Female; Fluorodeoxyglucose F18; Follow-Up Studies; Humans; Levodopa - therapeutic use; Male; Medical sciences; Methoxyhydroxyphenylglycol - analogs & derivatives; Methoxyhydroxyphenylglycol - blood; Methoxyhydroxyphenylglycol - cerebrospinal fluid; Middle Aged; Multiple System Atrophy - blood; Multiple System Atrophy - cerebrospinal fluid; Multiple System Atrophy - diagnostic imaging; Multiple System Atrophy - drug therapy; Neurology; Original; Parkinsonian Disorders - cerebrospinal fluid; Parkinsonian Disorders - diagnostic imaging; Parkinsonian Disorders - drug therapy; Positron-Emission Tomography; Pure Autonomic Failure - blood; Pure Autonomic Failure - cerebrospinal fluid; Pure Autonomic Failure - diagnostic imaging; Pure Autonomic Failure - drug therapy; ROC Curve
• ISSN: 0006-8950; 1460-2156
• DOI: 10.1093/brain/aws055

Central catecholamine deficiency characterizes α-synucleinopathies such as Parkinson's disease. We hypothesized that cerebrospinal fluid levels of neuronal metabolites of catecholamines provide neurochemical biomarkers of these disorders. To test this hypothesis we measured cerebrospinal fluid levels of catechols including dopamine, norepinephrine and their main respective neuronal metabolites dihydroxyphenylacetic acid and dihydroxyphenylglycol in Parkinson's disease and two other synucleinopathies, multiple system atrophy and pure autonomic failure. Cerebrospinal fluid catechols were assayed in 146 subjects-108 synucleinopathy patients (34 Parkinson's disease, 54 multiple system atrophy, 20 pure autonomic failure) and 38 controls. In 14 patients cerebrospinal fluid was obtained before or within 2 years after the onset of parkinsonism. The Parkinson's disease, multiple system atrophy and pure autonomic failure groups all had lower cerebrospinal fluid dihydroxyphenylacetic acid [0.86 ± 0.09 (SEM), 1.00 ± 0.09, 1.32 ± 0.12 nmol/l] than controls (2.15 ± 0.18 nmol/l; P