Neurodegeneration in the cortical sulcus is a feature of chronic traumatic encephalopathy and associated with repetitive head impacts.

Neurodegeneration is a seminal feature of many neurological disorders. Chronic traumatic encephalopathy (CTE) is caused by repetitive head impacts (RHI) and is characterized by sulcal tau pathology. However, quantitative assessments of regional neurodegeneration in CTE have not been described.

Duration of Ice Hockey Play and Chronic Traumatic Encephalopathy.

Importance: Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impacts (RHIs). Prior research suggests a dose-response association between American football play duration and CTE risk and severity, but this association has not been studied for ice hockey.

Objective: To investigate associations of duration of ice hockey play with CTE diagnosis and severity, functional status, and dementia.

SHARD: an improved method for staining and visualizing multiplex immunofluorescence in optically cleared postmortem human brain tissue.

Postmortem human brain tissue is a critical resource for studying neurodegenerative disease, providing critical insights into cellular morphology, pathology, and network connectivity. To improve standard microscopy and enable high-resolution, three-dimensional (3D) images of tissues at the subcellular level, tissue-clearing methods have been developed. These 3D images allow for the analysis of large regions of interest and can be used to study structural and spatial changes that occur during neurodegeneration.

Clinical and Neuropathological Correlates of Substance Use in American Football Players.

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy more frequently found in deceased former football players. CTE has heterogeneous clinical presentations with multifactorial causes. Previous literature has shown substance use (alcohol/drug) can contribute to Alzheimer's disease and related tauopathies pathologically and clinically.

Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood.

The molecular pathology of stress-related disorders remains elusive. Our brain multiregion, multiomic study of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) included the central nucleus of the amygdala, hippocampal dentate gyrus, and medial prefrontal cortex (mPFC). Genes and exons within the mPFC carried most disease signals replicated across two independent cohorts.

Repetitive head impacts induce neuronal loss and neuroinflammation in young athletes.

Repetitive head impacts (RHI) sustained from contact sports are the largest risk factor for chronic traumatic encephalopathy (CTE). Currently, CTE can only be diagnosed after death and the multicellular cascade of events that trigger initial hyperphosphorylated tau (p-tau) deposition remain unclear. Further, the symptoms endorsed by young individuals with early disease are not fully explained by the extent of p-tau deposition, severely hampering development of therapeutic interventions.

Lack of Association of Informant-Reported Traumatic Brain Injury and Chronic Traumatic Encephalopathy.

Repetitive head impacts (RHIs) from football are associated with the neurodegenerative tauopathy chronic traumatic encephalopathy (CTE). It is unclear whether a history of traumatic brain injury (TBI) is sufficient to precipitate CTE neuropathology. We examined the association between TBI and CTE neuropathology in 580 deceased individuals exposed to RHIs from football.

Cognitive, functional, and neuropsychiatric correlates of regional tau pathology in autopsy-confirmed chronic traumatic encephalopathy.

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by hyperphosphorylated tau (p-tau) accumulation. The clinical features associated with CTE pathology are unclear. In brain donors with autopsy-confirmed CTE, we investigated the association of CTE p-tau pathology density and location with cognitive, functional, and neuropsychiatric symptoms.

Optimal blood tau species for the detection of Alzheimer's disease neuropathology: an immunoprecipitation mass spectrometry and autopsy study.

Plasma-to-autopsy studies are essential for validation of blood biomarkers and understanding their relation to Alzheimer's disease (AD) pathology. Few such studies have been done on phosphorylated tau (p-tau) and those that exist have made limited or no comparison of the different p-tau variants. This study is the first to use immunoprecipitation mass spectrometry (IP-MS) to compare the accuracy of eight different plasma tau species in predicting autopsy-confirmed AD.

Unlocking the Hidden Depths: Multi-Modal Integration of Imaging Mass Spectrometry-Based and Molecular Imaging Techniques.

Multimodal imaging (MMI) has emerged as a powerful tool in clinical research, combining different imaging modes to acquire comprehensive information and enabling scientists and surgeons to study tissue identification, localization, metabolic activity, and molecular discovery, thus aiding in disease progression analysis. While multimodal instruments are gaining popularity, challenges such as non-standardized characteristics, custom software, inadequate commercial support, and integration issues with other instruments need to be addressed. The field of multimodal imaging or multiplexed imaging allows for simultaneous signal reproduction from multiple imaging strategies.

Single-Nucleus Transcriptome Profiling of Dorsolateral Prefrontal Cortex: Mechanistic Roles for Neuronal Gene Expression, Including the 17q21.31 Locus, in PTSD Stress Response.

Objective: Multidisciplinary studies of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) implicate the dorsolateral prefrontal cortex (DLPFC) in disease risk and pathophysiology. Postmortem brain studies have relied on bulk-tissue RNA sequencing (RNA-seq), but single-cell RNA-seq is needed to dissect cell-type-specific mechanisms. The authors conducted the first single-nucleus RNA-seq postmortem brain study in PTSD to elucidate disease transcriptomic pathology with cell-type-specific resolution.

Three dimensional evaluation of cerebrovascular density and branching in chronic traumatic encephalopathy.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHI) and characterized by perivascular accumulations of hyperphosphorylated tau protein (p-tau) at the depths of the cortical sulci. Studies of living athletes exposed to RHI, including concussive and nonconcussive impacts, have shown increased blood-brain barrier permeability, reduced cerebral blood flow, and alterations in vasoreactivity. Blood-brain barrier abnormalities have also been reported in individuals neuropathologically diagnosed with CTE.

Decreased myelin proteins in brain donors exposed to football-related repetitive head impacts.

American football players and other individuals exposed to repetitive head impacts can exhibit a constellation of later-life cognitive and neuropsychiatric symptoms. While tau-based diseases such as chronic traumatic encephalopathy can underpin certain symptoms, contributions from non-tau pathologies from repetitive head impacts are increasingly recognized. We examined cross-sectional associations between myelin integrity using immunoassays for myelin-associated glycoprotein and proteolipid protein 1 with risk factors and clinical outcomes in brain donors exposed to repetitive head impacts from American football.

Chronic traumatic encephalopathy (CTE): criteria for neuropathological diagnosis and relationship to repetitive head impacts.

Over the last 17 years, there has been a remarkable increase in scientific research concerning chronic traumatic encephalopathy (CTE). Since the publication of NINDS-NIBIB criteria for the neuropathological diagnosis of CTE in 2016, and diagnostic refinements in 2021, hundreds of contact sport athletes and others have been diagnosed at postmortem examination with CTE. CTE has been reported in amateur and professional athletes, including a bull rider, boxers, wrestlers, and American, Canadian, and Australian rules football, rugby union, rugby league, soccer, and ice hockey players.

Genetic Risk for Alzheimer Disease and Plasma Tau Are Associated With Accelerated Parietal Cortex Thickness Change in Middle-Aged Adults.

Background And Objectives: Neuroimaging and biomarker studies in Alzheimer disease (AD) have shown well-characterized patterns of cortical thinning and altered biomarker concentrations of tau and β-amyloid (Aβ). However, earlier identification of AD has great potential to advance clinical care and determine candidates for drug trials. The extent to which AD risk markers relate to cortical thinning patterns in midlife is unknown.