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. 2021 Jun 29;13(1):e12214.
doi: 10.1002/dad2.12214. eCollection 2021.

Diagnostic and prognostic performance of CSF α-synuclein in prion disease in the context of rapidly progressive dementia

Andrea Mastrangelo  1 , Simone Baiardi  1   2 , Corrado Zenesini  2 , Anna Poleggi  3 , Angela Mammana  2 , Barbara Polischi  2 , Anna Ladogana  3 , Sabina Capellari  1   4 , Piero Parchi  1   2
Affiliations

Diagnostic and prognostic performance of CSF α-synuclein in prion disease in the context of rapidly progressive dementia

Andrea Mastrangelo et al. Alzheimers Dement (Amst). .

Abstract

Introduction: Surrogate cerebrospinal fluid (CSF) biomarkers of neurodegeneration still have a central role in the first-line screening of patients with suspected Creutzfeldt-Jakob disease (CJD). Recently, CSF α-synuclein, a marker of synaptic damage, showed a close to optimal performance in distinguishing between CJD and other neurodegenerative dementias.

Methods: We evaluated the diagnostic value of CSF α-synuclein in patients with prion disease, non-prion rapidly progressive dementias, and non-neurodegenerative controls. Additionally, we studied its distribution across the different prion disease subtypes and evaluated its association with survival.

Results: CSF α-synuclein levels were significantly higher in patients with prion disease than in the other groups but showed a lower diagnostic value than CSF total tau or 14-3-3. Moreover, CSF α-synuclein was significantly associated with survival in the whole prion cohort and the most frequent clinicopathological subtypes.

Discussion: In the clinical setting, CSF α-synuclein does not exceed the diagnostic performance of currently used surrogate markers, but it might constitute a robust prognostic indicator.

Keywords: Creutzfeldt‐Jakob disease; alpha‐synuclein; cerebrospinal fluid; diagnosis; fatal familial insomnia; prognosis; rapidly progressive dementias.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
CSF α‐synuclein levels in the diagnostic groups and ROC curves for CSF α‐synuclein and other CSF surrogate biomarkers. A, CSF α‐synuclein values in prion disease, non‐prion rapidly progressive dementia (non‐prion RPD), and controls. B, CSF α‐synuclein levels in sporadic Creutzfeldt‐Jakob disease (sCJD) subtypes MM(V)1, VV2, MV2K, and MM(V)2C, FFI and genetic Creutzfeldt‐Jakob disease (gCJD) with E200K and V210I mutations. Thick lines represent medians and interquartile range. CSF α‐synuclein values are expressed in logarithmic scale. See the main text (section 3.3) for all the P‐values (Kruskal‐Wallis followed by Dunn‐Bonferroni post hoc test). C, ROC curves for CSF α‐synuclein (blue), CSF total tau (red), CSF 14‐3‐3 (green), and CSF NfL (black) in the comparison between patients with prion disease and those with non‐prion RPD. α‐syn, alpha‐synuclein; CSF, cerebrospinal fluid; FFI, fatal familial insomnia; NfL, neurofilament light chain; ROC, receiver operating characteristic; t‐tau, total tau
FIGURE 2
FIGURE 2
Prognostic value of CSF α‐syn. Survival curve in patients of the whole prion cohort according to the values of CSF α‐synuclein. α‐syn, alpha‐synuclein; CSF, cerebrospinal fluid
See this image and copyright information in PMC

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