Variation in TMEM106B in chronic traumatic encephalopathy
Abstract The genetic basis of chronic traumatic encephalopathy (CTE) is poorly understood. Variation in transmembrane protein 106B (TMEM106B) has been associated with enhanced neuroinflammation during aging and with TDP-43-related neurodegenerative disease, and rs3173615, a missense coding SNP in TM...
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-11-01
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| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40478-018-0619-9 |
| _version_ | 1817993731272343552 |
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| author | Jonathan D. Cherry Jesse Mez John F. Crary Yorghos Tripodis Victor E. Alvarez Ian Mahar Bertrand R. Huber Michael L. Alosco Raymond Nicks Bobak Abdolmohammadi Patrick T. Kiernan Laney Evers Sarah Svirsky Katharine Babcock Hannah M. Gardner Gaoyuan Meng Christopher J. Nowinski Brett M. Martin Brigid Dwyer Neil W. Kowall Robert C. Cantu Lee E. Goldstein Douglas I. Katz Robert A. Stern Lindsay A. Farrer Ann C. McKee Thor D. Stein |
| author_facet | Jonathan D. Cherry Jesse Mez John F. Crary Yorghos Tripodis Victor E. Alvarez Ian Mahar Bertrand R. Huber Michael L. Alosco Raymond Nicks Bobak Abdolmohammadi Patrick T. Kiernan Laney Evers Sarah Svirsky Katharine Babcock Hannah M. Gardner Gaoyuan Meng Christopher J. Nowinski Brett M. Martin Brigid Dwyer Neil W. Kowall Robert C. Cantu Lee E. Goldstein Douglas I. Katz Robert A. Stern Lindsay A. Farrer Ann C. McKee Thor D. Stein |
| author_sort | Jonathan D. Cherry |
| collection | DOAJ |
| description | Abstract The genetic basis of chronic traumatic encephalopathy (CTE) is poorly understood. Variation in transmembrane protein 106B (TMEM106B) has been associated with enhanced neuroinflammation during aging and with TDP-43-related neurodegenerative disease, and rs3173615, a missense coding SNP in TMEM106B, has been implicated as a functional variant in these processes. Neuroinflammation and TDP-43 pathology are prominent features in CTE. The purpose of this study was to determine whether genetic variation in TMEM106B is associated with CTE risk, pathological features, and ante-mortem dementia. Eighty-six deceased male athletes with a history of participation in American football, informant-reported Caucasian, and a positive postmortem diagnosis of CTE without comorbid neurodegenerative disease were genotyped for rs3173615. The minor allele frequency (MAF = 0.42) in participants with CTE did not differ from previously reported neurologically normal controls (MAF = 0.43). However, in a case-only analysis among CTE cases, the minor allele was associated with reduced phosphorylated tau (ptau) pathology in the dorsolateral frontal cortex (DLFC) (AT8 density, odds ratio [OR] of increasing one quartile = 0.42, 95% confidence interval [CI] 0.22–0.79, p = 0.008), reduced neuroinflammation in the DLFC (CD68 density, OR of increasing one quartile = 0.53, 95% CI 0.29–0.98, p = 0.043), and increased synaptic protein density (β = 0.306, 95% CI 0.065–0.546, p = 0.014). Among CTE cases, TMEM106B minor allele was also associated with reduced ante-mortem dementia (OR = 0.40, 95% CI 0.16–0.99, p = 0.048), but was not associated with TDP-43 pathology. All case-only models were adjusted for age at death and duration of football play. Taken together, variation in TMEM106B may have a protective effect on CTE-related outcomes. |
| first_indexed | 2024-04-14T01:43:41Z |
| format | Article |
| id | doaj.art-00003741594643f4996e2555a01e03c7 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-04-14T01:43:41Z |
| publishDate | 2018-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-00003741594643f4996e2555a01e03c72022-12-22T02:19:37ZengBMCActa Neuropathologica Communications2051-59602018-11-01611910.1186/s40478-018-0619-9Variation in TMEM106B in chronic traumatic encephalopathyJonathan D. Cherry0Jesse Mez1John F. Crary2Yorghos Tripodis3Victor E. Alvarez4Ian Mahar5Bertrand R. Huber6Michael L. Alosco7Raymond Nicks8Bobak Abdolmohammadi9Patrick T. Kiernan10Laney Evers11Sarah Svirsky12Katharine Babcock13Hannah M. Gardner14Gaoyuan Meng15Christopher J. Nowinski16Brett M. Martin17Brigid Dwyer18Neil W. Kowall19Robert C. Cantu20Lee E. Goldstein21Douglas I. Katz22Robert A. Stern23Lindsay A. Farrer24Ann C. McKee25Thor D. Stein26Boston University Alzheimer’s Disease and CTE Center, Boston University School of MedicineBoston University Alzheimer’s Disease and CTE Center, Boston University School of MedicineDepartment of Pathology, Fishberg Department of Neuroscience, Friedman Brain Institute, Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai SchoolDepartment of Biostatistics, Boston University School of Public HealthBoston University Alzheimer’s Disease and CTE Center, Boston University School of MedicineBoston University Alzheimer’s Disease and CTE Center, Boston University School of MedicineBoston University Alzheimer’s Disease and CTE Center, Boston University School of MedicineBoston University Alzheimer’s Disease and CTE Center, Boston University School of MedicineDepartment of Veterans Affairs Medical CenterBoston University Alzheimer’s Disease and CTE Center, Boston University School of MedicineBoston University Alzheimer’s Disease and CTE Center, Boston University School of MedicineBoston University Alzheimer’s Disease and CTE Center, Boston University School of MedicineBoston University Alzheimer’s Disease and CTE Center, Boston University School of MedicineBoston University Alzheimer’s Disease and CTE Center, Boston University School of MedicineVA Boston Healthcare SystemVA Boston Healthcare SystemBoston University Alzheimer’s Disease and CTE Center, Boston University School of MedicineDepartment of Biostatistics, Boston University School of Public HealthDepartment of Neurology, Boston University School of MedicineBoston University Alzheimer’s Disease and CTE Center, Boston University School of MedicineDepartment of Anatomy and Neurobiology, Boston University School of MedicineBoston University Alzheimer’s Disease and CTE Center, Boston University School of MedicineDepartment of Neurology, Boston University School of MedicineBoston University Alzheimer’s Disease and CTE Center, Boston University School of MedicineDepartment of Neurology, Boston University School of MedicineBoston University Alzheimer’s Disease and CTE Center, Boston University School of MedicineBoston University Alzheimer’s Disease and CTE Center, Boston University School of MedicineAbstract The genetic basis of chronic traumatic encephalopathy (CTE) is poorly understood. Variation in transmembrane protein 106B (TMEM106B) has been associated with enhanced neuroinflammation during aging and with TDP-43-related neurodegenerative disease, and rs3173615, a missense coding SNP in TMEM106B, has been implicated as a functional variant in these processes. Neuroinflammation and TDP-43 pathology are prominent features in CTE. The purpose of this study was to determine whether genetic variation in TMEM106B is associated with CTE risk, pathological features, and ante-mortem dementia. Eighty-six deceased male athletes with a history of participation in American football, informant-reported Caucasian, and a positive postmortem diagnosis of CTE without comorbid neurodegenerative disease were genotyped for rs3173615. The minor allele frequency (MAF = 0.42) in participants with CTE did not differ from previously reported neurologically normal controls (MAF = 0.43). However, in a case-only analysis among CTE cases, the minor allele was associated with reduced phosphorylated tau (ptau) pathology in the dorsolateral frontal cortex (DLFC) (AT8 density, odds ratio [OR] of increasing one quartile = 0.42, 95% confidence interval [CI] 0.22–0.79, p = 0.008), reduced neuroinflammation in the DLFC (CD68 density, OR of increasing one quartile = 0.53, 95% CI 0.29–0.98, p = 0.043), and increased synaptic protein density (β = 0.306, 95% CI 0.065–0.546, p = 0.014). Among CTE cases, TMEM106B minor allele was also associated with reduced ante-mortem dementia (OR = 0.40, 95% CI 0.16–0.99, p = 0.048), but was not associated with TDP-43 pathology. All case-only models were adjusted for age at death and duration of football play. Taken together, variation in TMEM106B may have a protective effect on CTE-related outcomes.http://link.springer.com/article/10.1186/s40478-018-0619-9Chronic traumatic encephalopathyTMEM106BNeuroinflammationFootballTraumatic brain injuryTau |
| spellingShingle | Jonathan D. Cherry Jesse Mez John F. Crary Yorghos Tripodis Victor E. Alvarez Ian Mahar Bertrand R. Huber Michael L. Alosco Raymond Nicks Bobak Abdolmohammadi Patrick T. Kiernan Laney Evers Sarah Svirsky Katharine Babcock Hannah M. Gardner Gaoyuan Meng Christopher J. Nowinski Brett M. Martin Brigid Dwyer Neil W. Kowall Robert C. Cantu Lee E. Goldstein Douglas I. Katz Robert A. Stern Lindsay A. Farrer Ann C. McKee Thor D. Stein Variation in TMEM106B in chronic traumatic encephalopathy Acta Neuropathologica Communications Chronic traumatic encephalopathy TMEM106B Neuroinflammation Football Traumatic brain injury Tau |
| title | Variation in TMEM106B in chronic traumatic encephalopathy |
| title_full | Variation in TMEM106B in chronic traumatic encephalopathy |
| title_fullStr | Variation in TMEM106B in chronic traumatic encephalopathy |
| title_full_unstemmed | Variation in TMEM106B in chronic traumatic encephalopathy |
| title_short | Variation in TMEM106B in chronic traumatic encephalopathy |
| title_sort | variation in tmem106b in chronic traumatic encephalopathy |
| topic | Chronic traumatic encephalopathy TMEM106B Neuroinflammation Football Traumatic brain injury Tau |
| url | http://link.springer.com/article/10.1186/s40478-018-0619-9 |
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