Cerebrospinal α-synuclein in α-synuclein aggregation disorders: tau/α-synuclein ratio as potential biomarker for dementia with Lewy bodies

Several studies have addressed the utility of cerebrospinal (CSF) alpha-synuclein levels as a potential biomarker of alpha-synuclein aggregation disorders. However, its relevance in the differential diagnostic context of neurodegenerative and movement disorders is still a contentious subject. Here, we report total CSF alpha-synuclein levels in a cohort of clinically diagnosed alpha-synuclein-related disorders encompassing Parkinson's disease, Parkinson's disease dementia, dementia with Lewy bodies and multiple system atrophy in comparison to essential tremor and neurological control cases. alpha-synuclein levels in alpha-synuclein-related disorders were significantly lower than in controls (p < 0.001). However, in the differential diagnostic context, only Parkinson's disease cases presented significant lower alpha-synuclein levels compared to essential tremor and neurological controls. In cases with clinically diagnosed alpha-synuclein pathology, CSF alpha-synuclein levels showed a moderate positive correlation with CSF tau and p-tau, but not with A beta 42 levels. Due to elevated CSF tau levels in dementia with Lewy bodies samples, tau/alpha-synuclein ratio showed a good clinical accuracy in discriminating controls from dementia with Lewy bodies cases (AUC = 0.8776) compared to single alpha-synuclein (AUC = 0.7192) and tau (AUC = 0.7739) levels. In conclusion, alpha-synuclein alone lacks of clinical value as a biomarker of alpha-synuclein-related disorders, but in combination with total tau, it may improve the diagnosis of dementia with Lewy bodies.