Transcriptome network analysis of chronic traumatic encephalopathy and Alzheimer's disease show altered expression of synaptotagmins associated with long-term potentiation

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that is associated with traumatic brain injury (TBI). CTE is known to share similar neuropathological features with Alzheimers disease (AD), but little is known about the molecular properties in CTE. To better understand the neuropathological mechanism of TBI-related disorders, we conducted transcriptome sequencing analysis of 8 CTE post-mortem human brain tissues. We also included 10 AD and 6 CTE with AD (CTE/AD) post-mortem human brain samples in order to characterize unique or common transcriptome signatures among head trauma-related disorders. Using the weighted gene co-expression network analysis (WGCNA) and principal component analysis (PCA), we found a similar distributions of CTE, CTE/AD and AD. Down-regulation of synaptotagmins showed common transcriptome signatures in CTE, CTE/AD and AD. Synaptotamins are known to act as a redundant mediator for AMPA receptor exocytosis during LTP. We observed down-regulation of genes that play a pivotal role in the LTP process, such as calcium/calmodulin-dependent protein kinase II (CaMKII), protein kinase A (PKA), protein kinase C (PKC) and a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. These results suggest that dysregulation of synaptotagmin affects the LTP process in head trauma-related diseases and it causes a variety symptoms of neurodegenerative disorders such as cognitive function, memory loss and depression.