In a study recently published in JAMA Neurology, researchers at the University of Pennsylvania (PA, USA) working in conjunction with the Parkinson’s Progression Markers Initiative (PPMI) reported that in comparison to healthy controls, entirely untreated early stage Parkinson’s disease (PD) patients had lower concentrations of CSF biomarkers. In addition, the biomarker tests suggest subtypes of PD, such as the postural instability-gait disturbance-dominant motor subtype, can be identified by measuring levels of CSF biomarkers.
The PPMI is an international observation clinical study sponsored by The Michael J. Fox Foundation for Parkinson’s Research. “Through PPMI, we are hoping to identify subgroups of Parkinson’s patients whose disease is likely to progress at a different rate, as early as possible,” said John Trojanowski, co-author of the study and co-leader of the Bioanalytics Core for the PPMI.
The researchers performed a cross-sectional study of the initial 102 PPMI research volunteers, including 63 drug-naïve patients with early PD and 39 healthy controls. INNO-BIA AlzBio3 immunoassays and ELISAs were used to measure the CSF biomarkers: Aβ1-42, total tau [T-tau], tau phosphorylated at threonine 181 [P-tau181], and α-synuclein. Clinical features such as motor, neuropsychiatric and cognitive assessments were also assessed according to the PPMI study protocol.
The results demonstrated lower levels of all measured biomarkers in the PD patients compared with the healthy controls; however, there was a marked overlap between groups. Lower CSF T-tau and α-synuclein concentrations were also associated with increased motor severity. In addition, low levels of Aβ1-42 and P-tau181 appeared to be linked to the postural instability-gait disturbance-dominant motor subtype, whereas this association was not observed in patients with the tremor-dominant or intermediate subtypes.
The study suggests that CSF biomarker tests have prognostic and diagnostic value in early stage PD. Researchers will continue to evaluate the use of these biomarkers using the entire PPMI cohort. The PPMI recently announced the launch of a pre-motor arm focussed on patients who do not have PD but do have one of the three potential risk factors; hyposmia, rapid eye movement sleep behavior disorder, or a mutation in the LRRK2 gene. It is hoped that this study will enable PD biomarkers to be identified before the symptoms begin. Ken Marek, principal investigator of PPMI and president and senior scientist at the Institute for Neurodegenerative Disorders (CT, USA) said, “Finding a biomarker for PD could mean earlier diagnosis of the disease and lead to new drugs that may delay or even prevent the onset of motor symptoms.”
Source: Kang JH, Irwin DJ, Chen-Plotkin AS et al. Association of cerebrospinal fluid β-Amyloid 1-42, T-tau, P-tau181, and α-Synuclein levels with clinical features of drug-naive patients with early Parkinson disease. JAMA Neurol. 2013. doi: 10.1001/jamaneurol.2013.3861. (2013) (Epub ahead of print); The Michael J. Fox Foundation launches new arm of Parkinson’s Progression Markers Initiative studying at-risk populations in Parkinson’s disease.