Blood neuroexosomal excitatory amino acid transporter-2 is associated with cognitive decline in Parkinson's disease with RBD

Bing Leng; Hairong Sun; Mengfan Li; Junwu Zhao; Xiaoxiao Liu; Ran Yao; Tengqun Shen; Zhenguang Li; Jinbiao Zhang

doi:10.3389/fnagi.2022.952368

Blood neuroexosomal excitatory amino acid transporter-2 is associated with cognitive decline in Parkinson's disease with RBD

Front Aging Neurosci. 2022 Aug 23:14:952368. doi: 10.3389/fnagi.2022.952368. eCollection 2022.

Authors

Bing Leng¹, Hairong Sun¹, Mengfan Li¹, Junwu Zhao¹, Xiaoxiao Liu¹, Ran Yao¹, Tengqun Shen¹, Zhenguang Li¹, Jinbiao Zhang¹

Affiliation

¹ Department of Neurology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China.

Abstract

Background: Rapid eye movement (REM) sleep behavior disorder (RBD) predicts cognitive decline in Parkinson's disease (PD) patients without dementia. However, underlying mechanisms remain unknown. Accumulating studies suggest glutamatergic system dysregulation is associated.

Objective: To examine the effect of RBD on the rate of cognitive decline in PD patients and investigate whether plasma levels of the neuroexosomal vesicular glutamate transporter-1 (VGLUT-1) and excitatory amino acid transporter-2 (EAAT-2) are altered in PD patients with RBD.

Methods: This study included 157 newly diagnosed cognitive normal PD patients and 70 healthy controls (HCs). Based on one-night polysomnography recordings, the PD subjects were divided into PD with and without RBD (PD-RBD and PD-nRBD) groups. All participants received a complete clinical and neuropsychological evaluation at baseline. Plasma levels of neuroexosomal VGLUT-1 and EAAT-2 were measured by ELISA kits. After a 3-year follow-up, we evaluated baseline plasma levels of neuroexosomal glutamate transporters in each group as a predictor of cognitive decline using MoCA score changes over 3 years in regression models.

Results: Plasma levels of neuron-derived exosomal EAAT-2 and VGLUT-1 were significantly lower in PD patients than in HCs. Plasma levels of neuroexosomal EAAT-2 were significantly lower in PD-RBD than PD-nRBD group at baseline. At the 3-year follow-up, PD-RBD patients presented greater cognitive decline. Lower baseline blood neuroexosomal EAAT-2 predicted cognitive decline over 3 years in PD-RBD patients (β = 0.064, P = 0.003).

Conclusion: These findings indicate that blood neuroexosomal EAAT-2 is associated with cognitive decline in PD with RBD.

Keywords: Parkinson’s disease; REM sleep behavior disorder; cognitive dysfunction; excitatory amino acid transporter-2; vesicular glutamate transporter-1.