Objective: To assess whether Progressive Sopranuclear Palsy (PSP) patients show, in CSF an alteration of catecholamine metabolites.

Background: It was reported previously that, consistent with dopamine norepinephrine depletion, Parkinson’s disease (PD) involves low cerebrospinal fluid (CSF) levels of 3,4-dihydrxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylglycol (DHPG) (Goldstein et al., Brain 2012). Here we explore the chance that non-synucleinopathic forms of parkinsonism, such as the tauopathy PSP share similar alterations.

Methods: Lumbar puncture was done on a hospital ward (at University Tor Vergata, Rome Italy), in the morning between 8 and 9 AM after the patients had fasted overnight. Dopamine receptor agonists were stopped at least 2 days before and MAO-B inhibitors discontinued for at least a few weeks.The first 4 mL of obtained CSF were used for routine laboratory analyses. The next 1.5-2 mL were aliquoted into 6-8 200 µL aliquots in plastic sample tubes. The samples were kept frozen continuously at -80 degrees centigrade until shipped to the NIH in dry ice. All the samples arrived frozen solid and were stored at -80 centigrade at the NIH until thawed for assays, which were done within 2 weeks of receipt. Since treatment with anti-Parkinsonian medications affects CSF levels of catechols, this study focused on CSF neurochemical data from patients who were not on any medications or had a long washout, so that CSF DOPA levels were less than 1000 pg/mL (5.1 nM).

Results: Among patients with CSF DOPA <1000 pg/mL, CSF DOPAC varied with patient group (F=8.4, p<0.0001) and was lower in PD than in controls (p=0.001) or AD patients (p=0.0002) as well as in PSP versus controls (p=0.003) or AD patients (p=0.001). Further, also CSF DHPG was lower in PD than in controls (p=0.0004) or AD patients (p=0.04) and lower in PSP than in controls (p=0.03) but not AD patients. CSF DHPG tended to be decreased in AD (p=0.054). Because of the small number of untreated PSP patients in this, our data should be considered preliminary. The results justify further investigation from a larger cohort to verify if facilitating the differentiation amongst phenotypes (i.e. PSP-RS and PSP-P).

Conclusions: In conclusion, low CSF DOPAC and DHPG are biomarkers of parkinsonism regardless of the underlying pathogenetic mechanism.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/low-cerebrospinal-fluid-34-dihydroxyphenylacetic-acid-and-34-dihydroxyphenylglycol-levels-are-biomarkers-of-parkinsonian-disorders-including-psp/