Longitudinal striatal dopamine transporter binding and cerebrospinal fluid alpha-synuclein, amyloid beta, total tau, and phosphorylated tau in Parkinson's disease

Abstract

BACKGROUND: Previous studies investigated CSF levels of alpha-synuclein (alpha-syn), amyloid-beta (Abeta1-42), total tau (t-tau), and phosphorylated tau (p-tau) with clinical progression of Parkinson's disease (PD). However, there is limited data on the association between CSF biomarkers and dopamine uptake status in PD. AIM: In the current study, we aim to investigate the longitudinal association between striatal dopaminergic neuronal loss assessed by dopamine active transporter single photon emission computerized tomography (DaTSCAN) imaging with CSF alpha-syn, t-tau, p-tau, and Abeta1-42. METHODS: A total of 413 early-stage PD patients and 187 healthy controls (HCs) from the PPMI. Striatal binding ratios (SBRs) of DaTSCAN images in caudate and putamen nuclei were calculated. We investigated the cross-sectional and longitudinal association between CSF biomarkers and dopamine uptake using partial correlation models adjusted for the effect of age, sex, and years of education over 24 months of follow-up. RESULTS: The level of CSF alpha-syn, Abeta1-42, t-tau, and p-tau was significantly higher in HCs compared to PD groups at any time point. We found that higher CSF alpha-syn was associated with a higher SBR score in the left caudate at baseline (P = 0.038) and after 12 months (P = 0.012) in PD patients. Moreover, SBR scores in the left caudate and CSF Abeta1-42 were positively correlated at baseline (P = 0.021), 12 months (P = 0.006), and 24 months (P = 0.014) in patients with PD. Our findings demonstrated that change in CSF Abeta1-42 was positively correlated with change in SBR score in the left caudate after 24 months in the PD group (P = 0.043). CONCLUSION: We found that cross-sectional levels of alpha-syn and Abeta1-42 could reflect the degree of dopaminergic neuron loss in the left caudate nucleus. Interestingly, longitudinal changes in CSF Abeta1-42 could predict the severity of left caudal dopaminergic neuron loss throughout the disease. This suggested that Abeta pathology might precede dopaminergic loss in striatal nuclei in this case left caudate and subsequently cognitive impairment in PD patients, although future studies are needed to confirm our results and expand the understanding of the pathophysiology of cognitive dysfunction in PD.