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Neurological Sciences

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13.10.2022 | Original Article

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

verfasst von: Fardin Nabizadeh, Kasra Pirahesh, Elham Ramezannezhad

Erschienen in: Neurological Sciences | Ausgabe 2/2023

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Abstract

Background

Previous studies investigated CSF levels of α-synuclein (α-syn), amyloid-β (Aβ1-42), 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 α-syn, t-tau, p-tau, and Aβ1-42.

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 α-syn, Aβ1-42, t-tau, and p-tau was significantly higher in HCs compared to PD groups at any time point. We found that higher CSF α-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 Aβ1-42 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 Aβ1-42 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 α-syn and Aβ1-42 could reflect the degree of dopaminergic neuron loss in the left caudate nucleus. Interestingly, longitudinal changes in CSF Aβ1-42 could predict the severity of left caudal dopaminergic neuron loss throughout the disease. This suggested that Aβ 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.

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Titel: Longitudinal striatal dopamine transporter binding and cerebrospinal fluid alpha-synuclein, amyloid beta, total tau, and phosphorylated tau in Parkinson’s disease
verfasst von: Fardin Nabizadeh
Kasra Pirahesh
Elham Ramezannezhad
Publikationsdatum: 13.10.2022
Verlag: Springer International Publishing
Erschienen in: Neurological Sciences / Ausgabe 2/2023
Print ISSN: 1590-1874
Elektronische ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-022-06440-x

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