Promising early findings from Parkinson’s biomarker study

By Eleanor McDermid, Senior medwireNews Reporter

Early results from the Parkinson’s Progression Markers Initiative suggest that some cerebrospinal fluid (CSF) biomarkers hold diagnostic and prognostic promise.

The researchers believe that two established Alzheimer’s disease biomarkers – β-amyloid 1-42 (Aβ1-42) and tau phosphorylated at threonine 181 (P-tau181) – may aid early identification of patients with the postural instability–gait disturbance (PIGD) subtype of Parkinson’s disease (PD).

“The significance of this finding is that the PIGD-PD motor subtype has been reported to progress more quickly, along both motor and nonmotor trajectories,” say study author Leslie Shaw (University of Pennsylvania, Philadelphia, USA) and team.

They say that, although preliminary, the findings are important because it is difficult to clinically establish PD subtype in many patients in the early stages of the disease.

“Since the data suggest that these CSF protein patterns may be able to differentiate between the various motor subtypes even in early stages of PD, they may turn out to be promising biomarkers of differential trajectories of PD progression,” writes the team in JAMA Neurology.

The findings come from data for the first 102 study participants: 63 drug-naïve patients with early-stage Parkinson’s disease and 39 demographically matched healthy controls. Overall, levels of Aβ1-42, P-tau181, total tau (T-tau), and the T-tau/Aβ1-42 ratio were significantly lower in patients than controls, as were levels of the Lewy body protein α-synuclein (α-syn). After multivariate adjustment Aβ1-42 and P-tau181 remained significantly associated with diagnosis, but the accuracy of these biomarkers for distinguishing between patients and controls was low.

The addition of other CSF, plasma, and genetic markers “will also likely be necessary to improve the diagnostic utility of the CSF biomarkers studied here,” say the researchers.

The team found that the two most promising biomarkers – Aβ1-42 and P-tau181 – were significantly lower in patients with PIGD-PD than in those with the tremor-dominant or intermediate subtypes. Indeed, the overall differences relative to controls were driven by patients with PIGD-PD, as biomarker levels in those with tremor-dominant or intermediate PD were no different to those in controls.

Of note, there was a strong correlation between α-syn levels and T-tau, not only in PD patients but also in the healthy controls. The association in patients is “consistent with the notion that the deposition of α-syn in the PD brain may cause the decrease of α-syn in CSF of patients with PD and also may inhibit the release of tau proteins into CSF by unknown molecular mechanisms,” say Shaw et al.

They believe the existence of the same correlation in controls is not contradictory, given the frequent finding of Lewy bodies in cognitively normal elderly people.

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