Objective: We hypothesize that CSF profiles of Aβ and Tau (total and phosphorylated) are associated with clinical subtypes and disease progression.

Background: Parkinson’s disease (PD) patients show a large phenotypic variability reflecting inter-individual pathologic heterogeneity. .This calls for prediction and progression biomarkers in order to monitor the course of neurodegeneration, and to establish endpoints for neuroprotective therapeutic strategies aiming to modify disease progression. Besides Lewy-body pathology, β-amyloid (Aβ) and Tau pathology as well as altered CSF levels of Aβ_1-42, total-Tau (t-Tau) and phosphorylated-Tau (p-Tau) have been reported. 

Methods:

We assessed CSF profiles of Aβ_1-42, t-Tau, and p-Tau in 342 sporadic PD patients and 124 healthy controls. A parenchymal Aβ probability score (PAP-score) was developed by combining Aβ and Tau profiles in order to predict clinical milestones.

Results:

PD patients showed lower levels of Aβ_1-42 and higher levels of t-Tau and p-Tau compared to healthy control individuals. Higher baseline levels of t-Tau were associated with cognitive impairment. This could be confirmed in a subgroup of patients longitudinally. PD patients with a high PAP-score were more likely to develop cognitive impairment earlier in the disease course.

Conclusions: In sporadic PD patients, low levels of Aβ_1-42 and high levels of Tau are associated with cognitive decline.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/tau-predicts-cognitive-impairment-in-a-prospective-longitudinal-csf-study-in-parkinsons-disease/