Lower Posttraumatic α-Synuclein Level Associated With Altered Default Mode Network Connectivity Following Acute Mild Traumatic Brain Injury

Abstract

This study aimed to investigate the changes of α-synuclein in serum and its relationship with default mode network (DMN) connectivity after acute mild traumatic brain injury (mild TBI). Fifty-two patients with mild TBI at the acute phase and 47 matched healthy controls were enrolled in the study. All participants received resting-state functional magnetic resonance imaging (fMRI) and neuropsychological assessments. Relations between the levels of α-synuclein in serum and clinical assessments were obtained using multivariate linear regression. Results showed that the patients with lower α-synuclein presented more complaints on post-concussion symptoms and depression. Moreover, patients with high levels of α-synuclein exhibited significantly decreased functional connectivity in the left precuneus and increased functional connectivity in both the left anterior cingulate cortex and ventro-medial prefrontal cortex (MPFC) compared with patients with low levels of α-synuclein. These findings supported that α-synuclein may modulate the functional connectivity within the DMN and suggest the feasibility of using α-synuclein as an objective biomarker for diagnosis and prognosis of mild TBI.

The Role of Blood Biomarkers for Magnetic Resonance Imaging Diagnosis of Traumatic Brain Injury

“…Ye et al showed that in TBI patients, high α-synuclein is associated with greater functional connectivity; this paradoxical finding may be related to a compensatory mechanism following brain injury that utilizes this presynaptic neuronal protein. Importantly, the low levels of α-synuclein not only predicted decreased functional connectivity, but also greater post-concussional symptoms [29]. This shows that α-synuclein may be important for an outcomes-based treatment approach.…”

“…α-Synuclein is a presynaptic neuronal protein seen in various forms of dementia. In 2019 Ye et al examined serum α-synuclein in 52 mTBI patients and 47 healthy controls using a multiplex assay (Luminex Corp, Austin, TX, USA) [29]. Patients were evaluated with functional MRI and comprehensive neuropsychological testing.…”

“…As α-synuclein is a presynaptic neuronal protein present in dementia, this finding may seem paradoxical. The authors suggest that the higher α-synuclein levels in patients with greater connectivity and better outcomes may be due to a compensatory mechanism whereas lower levels are due to lack of compensation [29].…”

Blood biomarkers of secondary outcomes following concussion: A systematic review

“…PPCS was measured continuously in 2 studies, where blood sample collection and cognitive testing was conducted at multiple timepoints (49,50). In 4 other studies, PPCS was defined as continuing to experience symptoms at 48 h, 6 days, 2 weeks, and 4 months post injury (49,(51)(52)(53).…”

Investigating the Activity of Alpha-synuclein Protein in Determining Neuronal Damage in Rats with Experimental Head Trauma

“…Fosforilasyon ve diğer yollarla aktive olan, presinaptik bölgede bulunan αsyn, sinaptik veziküllerin fizyolojisinde önemli bir rol oynar. Merkezi Sinir Sisteminde ağırlıklı olarak nöronlarda eksprese edilen 140 amino asitlik protein olan α-syn, bir dizi nörodejeneratif hastalıkta ayırt edici biyobelirteç olarak kullanılmaktadır 7 . Bu çalışmamızdaki amacımız sıçanlarda deneysel olarak oluşturulan farklı şiddetteki KT modellerinde erken dönemde serum α-syn seviyelerini incelemek ve acil serviste (AS), TBY tanısında BBT'ye alternatif olup olamayacağını araştırmaktır.…”