The utility of α-synuclein as biofluid marker in neurodegenerative diseases: a systematic review of the literature

Abstract

The discovery of α-synuclein (α-syn) as a major component of Lewy bodies, neuropathological hallmark of Parkinson's disease (PD), dementia with Lewy bodies and of glial inclusions in multiple system atrophy initiated the investigation of α-syn as a biomarker in cerebrospinal fluid (CSF). Due to the involvement of the periphery in PD the quantification of α-syn in peripheral fluids such as serum, plasma and saliva has been investigated as well. We review how the development of multiple assays for the quantification of α-syn has yielded novel insights into the variety of α-syn species present in the different fluids; the optimal preanalytical conditions required for robust quantification and the potential clinical value of α-syn as biomarker. We also suggest future approaches to use of CSF α-syn in neurodegenerative diseases.

Concomitant AD pathology affects clinical manifestation and survival in dementia with Lewy bodies

“…Furthermore, we did not routinely measure α-synuclein, the major pathological component of DLB, in CSF in this study. CSF α-synuclein as a biomarker is still a subject of intensive research and has not reached sufficient accuracy to be used in clinical practice 39. With reliable biomarkers for multiple pathologies, more insight into interactions between pathologies can be gained.…”

Cognitive decline in Parkinson disease

“…However, the DeNoPa study reported no change in α-synuclein or other CSF markers during a 24-month study period 99 . In addition to total α-synuclein, post-translationally modified forms of α-synuclein, including phosphorylated, nitrated and ubiquitylated forms, as well as oligomers, have been identified, and show some promise as markers of disease progression in PD 103–105 , but further research is needed to confirm their diagnostic and prognostic utility as markers for cognitive impairment in PD.…”

Cerebrospinal Fluid Alzheimer’s Disease Biomarkers Across the Spectrum of Lewy Body Diseases: Results from a Large Multicenter Cohort

“…On the other hand, the accuracy of CSF biomarkers for the differential diagnosis of α-synucleinopathies is less well demonstrated. A number of studies have evaluated the potential value of CSF α-synuclein as a diagnostic marker for Lewy body diseases (LBD), however, large variations in the absolute levels α-synuclein have been reported and the results were conflicting (see [11] for review).…”