학술논문
Beta-amyloid deposition in chronic traumatic encephalopathy
Original Paper
Original Paper
Document Type
Academic Journal
Author
Stein, Thor D.; Montenigro, Philip H.; Alvarez, Victor E.; Xia, Weiming; Crary, John F.; Tripodis, Yorghos; Daneshvar, Daniel H.; Mez, Jesse; Solomon, Todd; Meng, Gaoyuan; Kubilus, Caroline A.; Cormier, Kerry A.; Meng, Steven; Babcock, Katharine; Kiernan, Patrick; Murphy, Lauren; Nowinski, Christopher J.; Martin, Brett; Dixon, Diane; Stern, Robert A.; Cantu, Robert C.; Kowall, Neil W.; McKee, Ann C.
Source
Acta Neuropathologica. July 2015, Vol. 130 Issue 1, p21, 14 p.
Subject
Language
English
ISSN
0001-6322
Abstract
Author(s): Thor D. Stein[sup.1] [sup.2] [sup.3] [sup.4] , Philip H. Montenigro[sup.3] [sup.5] , Victor E. Alvarez[sup.3] [sup.6] , Weiming Xia[sup.2] , John F. Crary[sup.7] [sup.8] [sup.9] , Yorghos Tripodis[sup.10] [sup.11] [...]
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild traumatic brain injury. It is defined pathologically by the abnormal accumulation of tau in a unique pattern that is distinct from other tauopathies, including Alzheimer's disease (AD). Although trauma has been suggested to increase amyloid [beta] peptide (A[beta]) levels, the extent of A[beta] deposition in CTE has not been thoroughly characterized. We studied a heterogeneous cohort of deceased athletes and military veterans with neuropathologically diagnosed CTE (n = 114, mean age at death = 60) to test the hypothesis that A[beta] deposition is altered in CTE and associated with more severe pathology and worse clinical outcomes. We found that A[beta] deposition, either as diffuse or neuritic plaques, was present in 52 % of CTE subjects. Moreover, A[beta] deposition in CTE occurred at an accelerated rate and with altered dynamics in CTE compared to a normal aging population (OR = 3.8, p < 0.001). We also found a clear pathological and clinical dichotomy between those CTE cases with A[beta] plaques and those without. A[beta] deposition was significantly associated with the presence of the APOE [epsilon]4 allele (p = 0.035), older age at symptom onset (p < 0.001), and older age at death (p < 0.001). In addition, when controlling for age, neuritic plaques were significantly associated with increased CTE tauopathy stage ([beta] = 2.43, p = 0.018), co-morbid Lewy body disease (OR = 5.01, p = 0.009), and dementia (OR = 4.45, p = 0.012). A subset of subjects met the diagnostic criteria for both CTE and AD, and in these subjects both A[beta] plaques and total levels of A[beta]1-40 were increased at the depths of the cortical sulcus compared to the gyral crests. Overall, these findings suggest that A[beta] deposition is altered and accelerated in a cohort of CTE subjects compared to normal aging and that A[beta] is associated with both pathological and clinical progression of CTE independent of age. Electronic supplementary material The online version of this article (doi:10.1007/s00401-015-1435-y) contains supplementary material, which is available to authorized users.
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild traumatic brain injury. It is defined pathologically by the abnormal accumulation of tau in a unique pattern that is distinct from other tauopathies, including Alzheimer's disease (AD). Although trauma has been suggested to increase amyloid [beta] peptide (A[beta]) levels, the extent of A[beta] deposition in CTE has not been thoroughly characterized. We studied a heterogeneous cohort of deceased athletes and military veterans with neuropathologically diagnosed CTE (n = 114, mean age at death = 60) to test the hypothesis that A[beta] deposition is altered in CTE and associated with more severe pathology and worse clinical outcomes. We found that A[beta] deposition, either as diffuse or neuritic plaques, was present in 52 % of CTE subjects. Moreover, A[beta] deposition in CTE occurred at an accelerated rate and with altered dynamics in CTE compared to a normal aging population (OR = 3.8, p < 0.001). We also found a clear pathological and clinical dichotomy between those CTE cases with A[beta] plaques and those without. A[beta] deposition was significantly associated with the presence of the APOE [epsilon]4 allele (p = 0.035), older age at symptom onset (p < 0.001), and older age at death (p < 0.001). In addition, when controlling for age, neuritic plaques were significantly associated with increased CTE tauopathy stage ([beta] = 2.43, p = 0.018), co-morbid Lewy body disease (OR = 5.01, p = 0.009), and dementia (OR = 4.45, p = 0.012). A subset of subjects met the diagnostic criteria for both CTE and AD, and in these subjects both A[beta] plaques and total levels of A[beta]1-40 were increased at the depths of the cortical sulcus compared to the gyral crests. Overall, these findings suggest that A[beta] deposition is altered and accelerated in a cohort of CTE subjects compared to normal aging and that A[beta] is associated with both pathological and clinical progression of CTE independent of age. Electronic supplementary material The online version of this article (doi:10.1007/s00401-015-1435-y) contains supplementary material, which is available to authorized users.