Trefoil Factor 3, Cholinesterase and Homocysteine: Potential Predictors for Parkinson’s Disease Dementia and Vascular Parkinsonism Dementia in Advanced Stage

Abstract

Trefoil factor 3 (TFF3), cholinesterase activity (ChE activity) and homocysteine (Hcy) play critical roles in modulating recognition, learning and memory in neurodegenerative diseases, such as Parkinson’s disease dementia (PDD) and vascular parkinsonism with dementia (VPD). However, whether they can be used as reliable predictors to evaluate the severity and progression of PDD and VPD remains largely unknown. Methods: We performed a cross-sectional study that included 92 patients with PDD, 82 patients with VPD and 80 healthy controls. Serum levels of TFF3, ChE activity and Hcy were measured. Several scales were used to rate the severity of PDD and VPD. Receivers operating characteristic (ROC) curves were applied to map the diagnostic accuracy of PDD and VPD patients compared to healthy subjects. Results: Compared with healthy subjects, the serum levels of TFF3 and ChE activity were lower, while Hcy was higher in the PDD and VPD patients. These findings were especially prominent in male patients. The three biomarkers displayed differences between PDD and VPD sub-groups based on genders and UPDRS (III) scores’ distribution. Interestingly, these increased serum Hcy levels were significantly and inversely correlated with decreased TFF3/ChE activity levels. There were significant correlations between TFF3/ChE activity/Hcy levels and PDD/VPD severities, including motor dysfunction, declining cognition and mood/gastrointestinal symptoms. Additionally, ROC curves for the combination of TFF3, ChE activity and Hcy showed potential diagnostic value in discriminating PDD and VPD patients from healthy controls. Conclusions: Our findings suggest that serum TFF3, ChE activity and Hcy levels may underlie the pathophysiological mechanisms of PDD and VPD. As the race to find biomarkers or predictors for these diseases intensifies, a better understanding of the roles of TFF3, ChE activity and Hcy may yield insights into the pathogenesis of PDD and VPD.

Different Perivascular Space Burdens in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson’s Disease

“…Parkinson's disease patients frequently suffer from mild cognitive impairment (MCI) (MoCA score more than 21 and less than 26) (Litvan et al, 2012), who are at higher risk of developing dementia compared to PD patients with normal cognition (PD-NC) (Kehagia et al, 2010). Several lines of evidence suggested the inflammatory risk factors (Trefoil Factor 3,neutrophils,lymphocytes,et al) in PD may modulate underlying neurodegeneration particularly in relation to dementia (Stojkovic et al, 2018;Zou et al, 2018;Nicoletti et al, 2020;Wang et al, 2020). It is promising to detect MRI-visible EPVS burden as a marker of cognitive decline in PD.…”

Microtubule defects in mesenchymal stromal cells distinguish patients with Progressive Supranuclear Palsy

“…Among them, intracellular trafficking is emerging as a key regulator of diverse processes such as cell division, migration and secretion, thus confirming that MT dysfunction could be really detrimental for cells. Defects in the secretion pathways could be linked to many neurodegenerative disorders as suggested by recent evidences reporting changes in the serum levels of modulatory factors in patients affected by PD, MSA and AD . Notably, specific properties of MSCs cells include the secretion of a set of factors/molecules to the extracellular space, the so‐called secretome, whose crucial role in anti‐inflammatory response makes them a promising therapeutic tool .…”

Heavy Metal-Induced Cerebral Small Vessel Disease: Insights into Molecular Mechanisms and Possible Reversal Strategies

“…Adefegha et al have reported that oral administration of Cd for 21 days may increases brain cholinesterase (both AChE and BChE) along with Na + /K + -ATPase) and monoamine oxidase activity [179]. Cholinesterase and Na + /K + -ATPase have been demonstrated for their involvement in the neurodegenerative diseases and also have considerable pharmacological relevance [180,181]. As stated above, brain inflammation further favors the initiation and progression of different brain diseases including cerebrovascular diseases [182].…”