Objective: To investigate CSF neurogranin differences in participants with Parkinson disease (PD) and controls and to examine its association with motor and cognitive symptoms.

Background: PD is thought to be due to the accumulation of a-synuclein that can lead to synaptic dysfunction and neuronal damage. Impaired synaptic function in brain regions may contribute to variable clinical symptoms seen in PD. Neurogranin is a small protein involved in post-synaptic integrity and function. Few studies have examined CSF neurogranin in PD with contradictory results [1, 2].  We hypothesize that CSF neurogranin is reduced in PD and that it may relate to motor and cognitive symptoms.

Method: All participants, PD (n=190) and controls (n=48), were part of a single-center longitudinal study and completed a lumbar puncture for CSF protein analysis (a-synuclein, total tau,  Aβ-amyloid₄₂, and neurogranin). Participants also had clinical assessments of overall motor (Unified Parkinson’s Disease Rating Scale-III, UPDRS-III) and cognitive function (Clinical Dementia Rating – sum of boxes, CDR-SB).

Results: CSF neurogranin was significantly decreased (p<0.001) in participants with PD (n=190) versus controls (n = 48), even after accounting for age and sex.  We found a strong positive correlation (P<0.001) between neurogranin and α-syn (R²=0.66), total tau (R²=0.64), and a weaker correlation with Aβ42 (R²=0.17[PJ1] ) in PD. There was no correlation between neurogranin and disease duration of motor symptoms, motor impairment as measured by UPDRS-III, or cognitive function as measured by CDR-SB.

Conclusion: CSF neurogranin levels are decreased in PD and are not related to the severity of motor and cognitive symptoms.

References: 1. Hall, S., Janelidze, S., Zetterberg, H., Brix, B., Mattsson, N., Surova, Y., … & Hansson, O. (2020). Cerebrospinal fluid levels of neurogranin in Parkinsonian disorders. Movement Disorders, 35(3), 513-518.

2. Bereczki, E., Bogstedt, A., Höglund, K., Tsitsi, P., Brodin, L., Ballard, C., … & Aarsland, D. (2017). Synaptic proteins in CSF relate to Parkinson’s disease stage markers. npj Parkinson’s Disease, 3(1), 7.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/csf-neurogranin-levels-are-decreased-in-parkinson-disease/