Low levels of two dopamine-related molecules in cerebrospinal fluid can help identify patients in the early stages of preclinical Parkinson’s disease, a study suggests.
The study, “Cerebrospinal fluid biomarkers of central dopamine deficiency predict Parkinson’s disease,” was published in Parkinsonism & Related Disorders.
Parkinson’s disease is mainly recognized by its motor symptoms, such as uncontrolled tremors, gait difficulties, and slow movement. However, by the time these symptoms appear, a significant loss of brain cells sensitive to dopamine has already occurred.
Because of this, there is a need for sensitive markers of early brain cell loss that can be used to track disease progression.
DOPAC and DOPA are two dopamine-related molecules whose levels are reduced in patients with untreated Parkinson’s. However, it was not clear if measuring levels of both proteins could help identify asymptomatic, healthy people who are at risk of developing Parkinson’s disease.
A team led by David Goldstein, MD, PhD, principal investigator at the National Institutes of Health, evaluated the levels of DOPAC and DOPA in cerebrospinal fluid samples collected from 26 at-risk people.
This analysis was integrated in the PDRisk prospective study of the National Institute of Neurological Disorders and Stroke (NINDS), which intends to identify early biomarkers of Parkinson’s disease.
Participants had to have at least three previously defined risk factors for Parkinson’s disease, including direct family history of the disease, loss of sense of smell, impaired sleep or abnormal sleep behavior, and low resting blood pressure.
Patients who were already showing signs of Parkinson’s-related motor symptoms during the enrollment phase were excluded from the study.
Of the 26 participants, four developed clinical Parkinson’s disease during the three-year follow-up period. These patients were found to have significantly lower levels of both DOPA and DOPAC in cerebrospinal fluid than the 22 participants who did not develop Parkinson’s for at least a mean follow-up of 4.2 years.
Researchers determined that the optimal cutoff value for defining low diagnostic DOPAC was 1.22 pmol/mL, which accurately predicted Parkinson’s risk in 84.1% of cases. For DOPA, the cutoff value was 2.63 pmol/mL, accurately predicting disease risk in 90.3% of cases.
These data suggest that early dopamine deficiency in at-risk individuals — defined by low DOPAC and DOPA levels — is linked to an increased likelihood of developing clinical Parkinson’s disease within three years.
Researchers believe the identified “predictive strength” reflects the important role of these neurochemical biomarkers in the underlying mechanisms of disease, suggesting that “neurochemical biomarkers of central dopamine deficiency identify the disease in a pre-clinical phase.”