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. In this study, we quantified three key neurodegenerative measures, including cortical thickness, neuronal density, and synaptic proteins, in contact sport athletes (n = 185) and non-athlete controls (n = 52) within the sulcal depth, middle, and gyral crest of the dorsolateral frontal cortex. Cortical thickness and neuronal density were decreased within the sulcus in CTE compared to controls (p's < 0.05). Measurements of synaptic proteins within the gyral crest showed a reduction of α-synuclein with CTE stage (p = 0.002) and variable changes in PSD-95 density. After adjusting for age, multiple linear regression models demonstrated a strong association between the duration of contact sports play and cortical thinning (p = 0.001) and neuronal loss (p = 0.032) within the sulcus. Additional regression models, adjusted for tau pathology, suggest that within the sulcus, the duration of play was associated with neuronal loss predominantly through tau pathology. In contrast, the association of duration of play with cortical thinning was minimally impacted by tau pathology. Overall, CTE is associated with cortical atrophy and a predominant sulcal neurodegeneration. Furthermore, the duration of contact sports play is associated with measures of neurodegeneration that are more severe in the cortical sulcus and may occur through tau-dependent and independent mechanisms.

Authors

Institutions

Publication Details

Journal
Acta Neuropathologica
Published
2024-12-06
DOI
https://doi.org/10.1007/s00401-024-02833-8
Citations
8
Primary Topic
Traumatic Brain Injury Research
Type
article
Field-Weighted Citation Impact
3.09

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

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

Camille D. Esnault, Nurgül Aytan, Sarah Horowitz, Morgane L M D Butler et al.
8 citations
Acta Neuropathologica
Traumatic Brain Injury Research
3.09
article

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

Camille D. Esnault, Nurgül Aytan, Sarah Horowitz, Morgane L M D Butler, Raymond Nicks, Lucas Fishbein, Thor D. Stein, Christopher J. Nowinski, Ann Carolyn McKee, Rebecca Mathias, Arsal Shah, Nicole Saltiel, Daniel Kirsch, Grace A. Rosen, Brett Martin, Bertrand R. Huber, Michael L. Alosco, Alexandra L. Boden, Daniel H. Daneshvar, Samantha Calderazzo, Weiming Xia, Sarah Daley, Elizabeth Spurlock, Yorghos Tripodis, Jesse Mez, Kerry A. Cormier, Gaoyuan Meng, Jonathan D. Cherry, Farwa Faheem, Victor E. Alvarez, Fatima Tu-Zahra, Suzie Marcus, Spiro Anthony Stathas
article en
8 citations

Abstract

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. In this study, we quantified three key neurodegenerative measures, including cortical thickness, neuronal density, and synaptic proteins, in contact sport athletes (n = 185) and non-athlete controls (n = 52) within the sulcal depth, middle, and gyral crest of the dorsolateral frontal cortex. Cortical thickness and neuronal density were decreased within the sulcus in CTE compared to controls (p's < 0.05). Measurements of synaptic proteins within the gyral crest showed a reduction of α-synuclein with CTE stage (p = 0.002) and variable changes in PSD-95 density. After adjusting for age, multiple linear regression models demonstrated a strong association between the duration of contact sports play and cortical thinning (p = 0.001) and neuronal loss (p = 0.032) within the sulcus. Additional regression models, adjusted for tau pathology, suggest that within the sulcus, the duration of play was associated with neuronal loss predominantly through tau pathology. In contrast, the association of duration of play with cortical thinning was minimally impacted by tau pathology. Overall, CTE is associated with cortical atrophy and a predominant sulcal neurodegeneration. Furthermore, the duration of contact sports play is associated with measures of neurodegeneration that are more severe in the cortical sulcus and may occur through tau-dependent and independent mechanisms.

Acta NeuropathologicaVol. 148(1)
Boston University (US), University of Massachusetts Lowell (US), Harvard University (US), Spaulding Rehabilitation Hospital (US), VA Boston Healthcare System (US), Massachusetts General Hospital (US), VA New England Healthcare System (US), Mass General Brigham (US)
U.S. Department of Defense, U.S. Department of Veterans Affairs, Alzheimer's Association, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Neurological Disorders and Stroke, Peer Reviewed Alzheimer’s Research Program
Good health and well-being
Openalex Percentile: Top 7%
Traumatic Brain Injury Research
3.09
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.