Objective: To evaluate whether concomitant Ab and Tau pathology might contribute to the prominent cognitive decline in PD_GBA.

Background: A considerable proportion of idiopathic Parkinson’s disease patients (PD_idiopathic), who present with dementia and the postural instability-gait disturbance motor subtype (PIGD) in their disease course, show Abeta and Tau pathology at autopsy in addition to the typical Lewy-body pathology. PD patients with GBA mutations (PD_GBA) present with even more cognitive impairment than seen in PDidiopathic.

Methods: CSF levels of Aβ1-42, t-Tau and p-Tau were assessed cross-sectionally as well as longitudinally (in a subgroup ) in 523 participants (29 PD_GBA, 343 PD_idiopathic, 27 DLB, and 124 healthy control participants (CON)) and analyzed in relation to clinical milestones, namely cognitive impairment and advanced disease stage including postural instability.

Results: Cross-sectional analyses revealed: (I) Lower levels of Aβ1-42 and higher levels of t-Tau are associated with worse cognitive performance in PD_idiopathic, a phenomenon which was not observed in PD_GBA.

Longitudinal analyses confirmed main findings from the cross-sectional part: (I) Higher levels of t-Tau at baseline predict lower MMSE scores over time in PD_idiopathic, but not in PD_GBA; (II) Lower levels of Aβ1-42 and/or higher levels of t-Tau and p-Tau are associated with a higher risk of developing cognitive impairment earlier in the disease process in PD_idiopathic, but not in PD_GBA. CSF levels of Aβ1-42, t-Tau, and p-Tau were similar between PD_GBA and DLB_GBA and resembled profiles seen in CON.

Conclusions: We conclude that the prominent cognitive decline in PD_GBA is not primarily associated with concomitant Abeta and Tau pathology.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/prospective-longitudinal-csf-measurements-and-cognitive-decline-in-gba-associated-parkinsonism-not-abeta-or-tau-but-lewy-body-pathology/