Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impacts (RHI), but the components of RHI exposure underlying this relationship are unclear. We ...create a position exposure matrix (PEM), composed of American football helmet sensor data, summarized from literature review by player position and level of play. Using this PEM, we estimate measures of lifetime RHI exposure for a separate cohort of 631 football playing brain donors. Separate models examine the relationship between CTE pathology and players' concussion count, athletic positions, years of football, and PEM-derived measures, including estimated cumulative head impacts, linear accelerations, and rotational accelerations. Only duration of play and PEM-derived measures are significantly associated with CTE pathology. Models incorporating cumulative linear or rotational acceleration have better model fit and are better predictors of CTE pathology than duration of play or cumulative head impacts alone. These findings implicate cumulative head impact intensity in CTE pathogenesis.
Introduction
Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impacts (RHI) typically sustained by contact sport athletes. Post‐translation ...modifications to tau in CTE have not been well delineated or compared to Alzheimer's disease (AD).
Methods
We measured phosphorylated tau epitopes within dorsolateral frontal cortex from post mortem brains with neither CTE nor AD (n = 108), CTE (n = 109), AD (n = 223), and both CTE and AD (n = 33).
Results
Levels of hyperphosphorylated tau (p‐tau)202, p‐tau231, and p‐tau396 were significantly increased in CTE. Total years of RHI exposure was significantly associated with increased p‐tau202 levels (P = .001), but not p‐tau396. Instead, p‐tau396 was most closely related to amyloid beta (Aβ)1‐42 levels (P < .001). The p‐tau202:p‐tau396 ratio was significantly increased in early and late CTE compared to AD.
Discussion
In frontal cortex, p‐tau202 is the most upregulated p‐tau species in CTE, while p‐tau396 is most increased in AD. p‐tau202 and p‐tau396 measurements may aid in developing biomarkers for disease.
Abstract
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head impacts (RHI) and characterized by perivascular hyperphosphorylated tau (p-tau) deposits. The ...role of vascular injury, blood-brain barrier leakage, and neuroinflammation in CTE pathogenesis is not well understood. We performed quantitative immunoassays for intercellular adhesion molecule 1 (ICAM1), vascular cellular adhesion molecule 1 (VCAM1), and C-reactive protein (CRP) within the postmortem dorsolateral frontal cortex of participants with and without a history of RHI and CTE (n = 156), and tested for associations with RHI, microgliosis, and tau pathology measures. Levels of vascular injury-associated markers ICAM1, VCAM1, and CRP were increased in CTE compared to RHI-exposed and -naïve controls. ICAM1 and CRP increased with RHI exposure duration (p < 0.01) and were associated with increased microglial density (p < 0.001) and tau pathology (AT8, p-tau396, p-tau202; p < 0.05). Histologically, there was significantly increased ICAM1 staining of the microvasculature, extracellular space, and astrocytes at the sulcal depths in high stage CTE compared to both low stage CTE and controls. Multifocal perivascular immunoreactivity for serum albumin was present in all RHI-exposed individuals. These findings demonstrate that vascular injury markers are associated with RHI exposure, duration, and microgliosis, are elevated in CTE, and increase with disease severity.
Exposure to repetitive head impacts (RHI) is associated with later-life cognitive symptoms and neuropathologies, including chronic traumatic encephalopathy (CTE). Cognitive decline in community ...cohorts is often due to multiple pathologies; however, the frequency and contributions of these pathologies to cognitive impairment in people exposed to RHI are unknown. Here, we examined the relative contributions of 13 neuropathologies to cognitive symptoms and dementia in RHI-exposed brain donors.
Neuropathologists examined brain tissue from 571 RHI-exposed donors and assessed for the presence of 13 neuropathologies, including CTE, Alzheimer disease (AD), Lewy body disease (LBD), and transactive response DNA-binding protein 43 (TDP-43) inclusions. Cognitive status was assessed by presence of dementia, Functional Activities Questionnaire, and Cognitive Difficulties Scale. Spearman rho was calculated to assess intercorrelation of pathologies. Additionally, frequencies of pathological co-occurrence were compared to a simulated distribution assuming no intercorrelation. Logistic and linear regressions tested associations between neuropathologies and dementia status and cognitive scale scores.
The sample age range was 18-97 years (median = 65.0, interquartile range = 46.0-76.0). Of the donors, 77.2% had at least one moderate-severe neurodegenerative or cerebrovascular pathology. Stage III-IV CTE was the most common neurodegenerative disease (43.1%), followed by TDP-43 pathology, AD, and hippocampal sclerosis. Neuropathologies were intercorrelated, and there were fewer unique combinations than expected if pathologies were independent (p < 0.001). The greatest contributors to dementia were AD, neocortical LBD, hippocampal sclerosis, cerebral amyloid angiopathy, and CTE.
In this sample of RHI-exposed brain donors with wide-ranging ages, multiple neuropathologies were common and correlated. Mixed neuropathologies, including CTE, underlie cognitive impairment in contact sport athletes. ANN NEUROL 2024;95:314-324.
Background
Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impact (RHI) exposure. We previously showed that duration of American football play ...is associated with risk and severity of CTE pathology. Helmet accelerometers have been used previously to examine frequency, linear acceleration, and rotational acceleration of hits sustained across youth, high school, and college football. Here we projected this data onto former American football playing brain donors to examine the relationship between cumulative frequency of hits, linear acceleration, and rotational acceleration during players’ athletic careers and CTE pathology.
Method
656 former American football playing brain donors from the Veterans Affairs‐Boston University‐Concussion Legacy Foundation Brain Bank were examined for CTE pathology and severity. Years and position of play at each level (youth, high school, college, professional) were acquired through retrospective clinical interviews with brain donors next‐of‐kin. From a literature search of studies using helmet accelerometers, we calculated the mean frequency of hits, linear acceleration (g‐force), and rotational acceleration (rad/sec2) for one year of play at each level‐position combination. These values were projected onto brain donors’ career exposure to derive cumulative frequency of head impacts (CHII), cumulative linear acceleration (CHII‐G), and cumulative rotational acceleration (CHII‐R). Separate logistic regression models examined the relationship of years of play, CHII, CHII‐G, and CHII‐R on CTE status and severity (low vs. high), adjusting for age at death.
Result
The mean (SD) age at death was 59.7 (20.1) and 451 (68.8%) had CTE pathology. Each cumulative measure was significantly associated with presence of CTE (p’s<.001) and severity of CTE (p’s<.001). Based on ROC analyses, CHII‐R (AUC=0.765, p<.001) and CHII‐G (AUC= 0.758, p<.001) performed significantly better than years of play (AUC=0.716) in classifying CTE pathology, and there was no difference between years of play and CHII (AUC=0.698, p=0.25). Similar relationships were observed for CTE severity. Model fit and cross‐validation statistics were also consistent (Table 2).
Conclusion
Among former American football playing brain donors, cumulative linear and rotational acceleration were better predictors of CTE pathology than duration of play or cumulative hits. The findings suggest head impact intensity is an important factor in developing CTE pathology.
Background
Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impact (RHI) exposure. The clinical presentation of CTE can be progressive, leading ...to cognitive and functional impairment. CTE presence and severity varies among those with similar RHI exposure, suggesting a role for other factors, genetics among them. Family history (FH) of dementia is a proxy of genetic risk of neurodegenerative disease, but its relationship with CTE is unknown. This study aimed to analyze the relationships between FH of dementia, quantitative tau pathology and functional impairment in brain donors at risk for CTE.
Method
558 brain donors from the Veterans Affairs‐Boston University‐Concussion Legacy Foundation Brain Bank with known RHI exposure through contact sports or military service were examined for CTE pathology. We performed digital quantification of AT8 immunostaining for tau pathology in the CA4 hippocampal subfield, a region disproportionately affected in CTE. First‐degree FH of dementia and the Functional Assessment Questionnaire (FAQ; 30 point scale), a validated measure of instrumental activities of daily living, were collected through telephone interviews with brain donors’ next‐of‐kin. Using a regression framework, we examined the direct and indirect relationships between FH of dementia, CA4 quantitative tau burden and FAQ score, adjusting for age and race.
Result
The mean (SD) age at death was 59.9 (20.4) and 362 (65%) had CTE pathology. In separate models, first‐degree FH of dementia was significantly associated with increased CA4 tau burden (β=0.27, p=0.01) and with increased FAQ score (β=2.11, p=0.02). Additionally, CA4 tau burden was associated with increased FAQ score (β=2.58, p=0.001). After adjusting for CA4 tau burden, the effect of first‐degree FH of dementia was reduced and no longer significant (β=.598, p=.663).
Conclusion
Among brain donors with RHI exposure, hippocampal CA4 tau burden may mediate the relationship between first‐degree FH of dementia and functional impairment. The findings suggest that the risk of CTE may be heritable and share etiologic mechanisms with other dementing illnesses.
As the demand of energy increases, renewable technologies are dominating in the recent years. Solar energy is one of the leading technologies in all of the renewable energies, due to its simplicity. ...In Pakistan, solar PV stand-alone units are mostly used to meet the energy requirements. During production of solar PV panel, it emits out lot of waste heat and it is necessary to calculate these emissions. This study investigates the complete Life Cycle Analysis (LCA) of two different types of solar panels which are locally available in Hyderabad markets. Complete modeling of Monocrystalline and Polycrystalline PV panels has been done by using GaBi software. This study shows the complete waste heat emissions during each stage of PV panel production. Two different types (Monocrystalline and Polycrystalline) of solar panels are designed under the dimensions of 1 m2. It is calculated that Monocrystalline PV panels are more efficient than Polycrystalline PV panels and they generates more units of electricity under same temperature conditions during its complete life. To enhance the electrical efficiency of solar PV panel, cooling system must be provided across it. The comparative analysis shows that Polycrystalline PV panels requires less amount of electrical energy as compare to Monocrystalline PV panels resulting in the reduction of waste heat emission. At the end of life, this study highlights the significance of recycling of solar panels which consider the reuse of the raw material. In this study, the combination of mechanical, thermal, and chemical process of recycling is considered. Recycling rate of solar PV panel has been assumed to be 90%. Recycling of raw material reduces the waste heat emission during purification process of raw material. Thus, cost is reduced and beneficial for environmental aspects. Result shows that recycling of solar PV panel is more beneficial than landfill for environmental and economic aspects.
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