Temporal trajectory of biofluid markers in Parkinson's disease

Full dynamics of biofluid biomarkers have been unknown in patients with Parkinson's disease (PD). Using data from 396 PD patients and 182 controls in the Parkinson's Progression Markers Initiative (PPMI) database, we estimated long-term temporal trajectories of CSF alpha -synuclein (alpha -syn), amyloid-beta (A beta), total tau (t-tau), phosphorylated tau (p-tau) and serum neurofilament light chain (NfL) by integrating function between the baseline levels and annual changes. At baseline, PD patients showed lower CSF alpha -syn, A beta, t-tau and p-tau levels than those of the controls. In all PD patients, CSF alpha -syn and A beta decreased in a negative exponential pattern before the onset of motor symptoms, whereas CSF t-tau and p-tau, and serum NfL increased. Patients with cognitive impairment exhibited faster decline of A beta and alpha -syn and faster rise of t-tau, p-tau and NfL, when compared to those without. Similarly, low A beta group showed earlier decline of alpha -syn, faster rise of t-tau, p-tau and NfL, and faster decline of cognitive performances, when compared to high A beta group. Our results suggest that longitudinal changes in biomarkers can be influenced by cognitive impairment and A beta burden at baseline. PD patients with A beta pathology may be associated with early appearance of alpha -synuclein pathology, rapid progression of axonal degeneration and neurodegeneration, and consequently greater cognitive decline.