Cho, Hyesun Hyeon, Seung Jae Shin, Jong-Yeon Alvarez, Victor E. Stein, Thor D. Lee, Junghee Kowall, Neil W. McKee, Ann C. Ryu, Hoon Seo, Jeong-Sun 2024-01-19T17:31:03Z 2024-01-19T17:31:03Z 2021-09-05 2020-06-01 2045-2322 https://pubs.kist.re.kr/handle/201004/118537 Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that is associated with repetitive traumatic brain injury (TBI). CTE is known to share similar neuropathological features with Alzheimer's 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 CTE including AD and CTE with AD (CTE/AD) post-mortem human brain samples. Through weighted gene co-expression network analysis (WGCNA) and principal component analysis (PCA), we characterized common and unique transcriptome signatures among CTE, CTE/AD, and AD. Interestingly, synapse signaling-associated gene signatures (such as synaptotagmins) were commonly down-regulated in CTE, CTE/AD, and AD. Quantitative real-time PCR (qPCR) and Western blot analyses confirmed that the levels of synaptotagmin 1 (SYT1) were markedly decreased in CTE and AD compared to normal. In addition, calcium/calmodulin-dependent protein kinase II (CaMKII), protein kinase A (PKA), protein kinase C (PKC), and AMPA receptor genes that play a pivotal role in memory function, were down-regulated in head trauma-related disorders. On the other hand, up-regulation of cell adhesion molecules (CAMs) associated genes was only found in CTE. Our results indicate that dysregulation of synaptic transmission- and memory function-related genes are closely linked to the pathology of head injury-related disorder and AD. Alteration of CAMs-related genes may be specific pathological markers for the CTE pathology. English NATURE PUBLISHING GROUP LONG-TERM POTENTIATION PROTEIN-KINASE-C CELL-ADHESION MOLECULES AMPA RECEPTOR EXOCYTOSIS ALZHEIMERS-DISEASE SYNAPTIC FUNCTION PHOSPHORYLATION CAMKII PKC ENCEPHALOPATHY Alterations of transcriptome signatures in head trauma-related neurodegenerative disorders Article 10.1038/s41598-020-65916-y 1 SCIENTIFIC REPORTS, v.10, no.1 SCIENTIFIC REPORTS 10 1 scie scopus 000540482200003 2-s2.0-85085880739 Multidisciplinary Sciences Science & Technology - Other Topics Article LONG-TERM POTENTIATION PROTEIN-KINASE-C CELL-ADHESION MOLECULES AMPA RECEPTOR EXOCYTOSIS ALZHEIMERS-DISEASE SYNAPTIC FUNCTION PHOSPHORYLATION CAMKII PKC ENCEPHALOPATHY