A Key Molecule in Blood is Linked to Cognitive Decline in Parkinson’s Patients with RBD

Published on August 23, 2022

Imagine your brain as a bustling city, with neurons communicating and sending important messages to keep everything running smoothly. But what if something disrupts this intricate network? In the case of Parkinson’s disease (PD) patients with rapid eye movement (REM) sleep behavior disorder (RBD), research suggests that a particular molecule called excitatory amino acid transporter-2 (EAAT-2) may play a role in cognitive decline. EAAT-2 is like a diligent mail carrier that helps regulate the levels of a neurotransmitter called glutamate, ensuring it doesn’t overwhelm the brain. However, in PD-RBD patients, the levels of EAAT-2 in their blood are significantly lower than in healthy individuals. This reduction in EAAT-2 is associated with greater cognitive decline over a three-year period. By understanding the role of EAAT-2 and its link to RBD and cognitive decline, researchers can potentially develop new interventions or therapeutic strategies to slow down or prevent cognitive impairment in PD patients. To dive deeper into this fascinating study, check out the original research article!

BackgroundRapid 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.ObjectiveTo 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.MethodsThis 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.ResultsPlasma 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).ConclusionThese findings indicate that blood neuroexosomal EAAT-2 is associated with cognitive decline in PD with RBD.

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