Objective: Our aim is to assess CSF levels of amyloid-β1-42 (Aβ1-42), T-Tau, threonine-181 phosphorilated tau (P-Tau) and α-synuclein (α-syn) as well as different ratios of these proteins as potential biomarkers for PD and cognitive impairment.

Background: There is a need for biological markers of PD as well as for the detection of early dementia in this disease. Despite several studies, no CSF biomarker has been yet validated.

Methods: 40 non-demented PD patients and 40 controls underwent lumbar puncture, and a comprehensive clinical and neuropsychological evaluation. According to their cognitive state patients were classified as cognitively normal (PDCN) (n=15) or with PD mild cognitive impairment (PD-MCI) (MDS-task force diagnostic criteria) (n=22). CSF levels of Aβ 1-42, T-Tau, P-Tau, and α-syn were measured by ELISA commercial kits.

Results: PD patients were on average older than controls (71.08 ± 6.28 vs. 68.21 ± 5.04; p=0.028). Adjusting for age, Aβ 1-42 levels (736.80 ± 239.15 vs. 1009.56 ± 487.43 pg/mL; p=0.048) were lower in PD patients than in controls and α-syn (877.62 ± 289.51 and 1188.36 ± 399.78 pg/mL p=0.068) levels showed a trend towards signification (lower levels in the former). Although T-Tau and P-Tau did not differ, PD patients showed higher ratios T-Tau/α-synuclein (p=0.001), P-Tau/α-synuclein (p<0.001), T-Tau/Aβ+α-synuclein (p=0.020), and P-Tau/Aß+α-synuclein (p=0.001) than controls. A ROC analysis showed an area under the curve for the P-Tau/α-synuclein ratio of 0.811 (95 % confidence interval: 0.713-0.910; p<0.001) for differentiating PD from controls. No differences in the proteins assessed or in their ratios were observed in the comparison between PDCN and PD-MCI. However, the T-Tau/Aβ ratio (r=-0.450; p=0.018) and the T-Tau/Aβ+α-synuclein ratio (R=-0.433; p=0.008) negatively correlated with the memory z score in PD patients.

Conclusions: The CSF study of the P-Tau/α-synuclein ratio might be useful as a biomarker in the diagnosis of PD. In addition, high T-Tau/Aβ and T-Tau/Aβ+α-synuclein ratios might also be useful in the early detection of cognitive deficits in PD, in particular in memory decline.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cerebrospinal-fluid-biomarkers-in-parkinsons-disease-and-associated-cognitive-impairment/