Introduction: Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder that is defined, neuropathologically, by the presence of aggregated hyperphosphorylated tau in the neurons and astrocytes of the perivascular area that is located deep in the cerebral sulci. The lesion is associated with repetitive brain trauma, from the spectrum of asymptomatic subconcussive head injury to grossly identifiable features of concussion. Although the diagnostic neuropathology of CTE is well-characterized, the precise mechanism that causes this to occur in CTE is not yet clearly elucidated. The features of hyperphosphorylated tau in CTE is quite similar with Alzheimer’s Disease (AD), as is the reduced expression of certain genes that are required to dephosphorylate tau, which is the putative culprit in the generation of amyloid aggregates and hyperphosphorylated tau.1 In comparison, Parkinson’s Disease (PD) is a neurodegenerative disease that is caused by accumulation of misfolded alpha-synuclein (α-syn) that causes the formation of intraneuronal Lewy Body aggregates. The pattern of accumulation for α-syn involves the olfactory bulb and the gut with progressive involvement of the posterior part of the brain.2 Despite establishing the presence of two different intraneuronal inclusions for CTE and PD, contact sports associated with the clinical spectrum of CTE has been shown to present with Parkinsonian features along with dementia. Mood disorders has been reported to occur in patients with these neurologic conditions. Several studies have documented that patients had a previous experience of traumatic brain injury prior to the diagnosis of Bipolar Disorder (BD). A review of electronic literature suggested that having an earlier diagnosis of BD increased the likelihood of having a diagnosis of PD in the future. Objectives: This research aimed to compare the over- and underexpressed genes in cases with Parkinson's Disease (PD), cases with Bipolar Disorder (BD), and cases with Chronic Traumatic Encephalopathy (CTE) versus normal controls. This was done to determine if parallel overexpression in certain genes may indicate the possible association at the level of gene expression. Identifying similar RNA sequence establishing gene expression may provide an insight to the relationship of the diseases in terms of pathobiological behavior. Determining the similar over- or underexpression pattern may provide an insight on the common pathobiologic mechanisms that may be the reason for the three disorders being associated by way of pre-morbid or co-morbid condition. Methodology: Transcripts from the public domain archive of the NCBI SRA were identified for the RNA sequence (RNAseq) of interest using the search string “Chronic Traumatic Encephalopathy”, “Bipolar Disorder”, and “Parkinson”. Only public domain transcriptome files of post-mortem brain samples labeled as RNAseq data extracted thru the Illumina platform that have a paired normal control were selected. A total of ten (10) cases for each disorder and thirty (30) normal subjects for control in the NCBI SRA RNAseq database with a whole exome sequence file that was available for public domain use was utilized for differential gene expression analysis. Results and Discussion: Among 21,122 identified genes from the RNAseq, the analysis was able to identify 26 genes exhibiting increased expression of up to >15 log2 fold change among cases with CTE, PD, and BD compared with normal controls. In contradistinction, only 6 well-described genes exhibited a decreased expression among cases with CTE and BD compared to normal controls. However, there were no identified genes that exhibited underexpression in cases with PD compared with normal controls. The identification of parallel gene overexpression among the CTE, BD, and PD groups with respect to structural integrity, cellular metabolism, homeo-stasis, and apoptosis may indicate a common pathway that have been initiated as part of the response to maintain tissue function or as a consequence of the underlying pathobiologic mechanism that caused the primary lesion. In comparison, the underexpressed genes detected in the CTE and BD cases compared to the normal controls and the PD cases may indicate the lack of genes that have a role in repressing the mRNA for protein coding. Conclusion The overexpression of genes responsible for homeostasis, regulation of inflammation, balance of apoptosis and anti-apoptosis, and maintenance of structural integrity among the CTE, BD, and PD groups indicate that there is an interrelated mechanism that serves converging pathways as part of the response to lesional- forming structures in the brain. The goal of studies such as this is to have a better understanding on the common pathways that explain the interrelatedness of brain disorders and the putative mechanism for being co-morbid and pre-morbid conditions of each other.
Chronic Traumatic Encephalopathy