Summary: A new study questions whether playing youth football leads to harmful protein buildup in the brain. Researchers examined 174 donated brains, including former high school and college players, and found no link between contact sports and excess tau protein in a key memory region.

Instead, the protein accumulation was tied to aging rather than head trauma. The findings urge caution in overinterpreting subtle brain changes as evidence of disease.

Key Facts

• No Link Found: Youth football players did not show increased p-tau in the CA2 hippocampus.
• Age Factor: Protein buildup in the brain was more strongly associated with aging than with sports.
• Caution Advised: Findings highlight challenges in distinguishing normal aging from disease in brain studies.

Source: Northwestern University

In recent years, some scientists and advocates have warned that playing contact sports like football and hockey may increase the risk of brain diseases like Alzheimer’s disease or chronic traumatic encephalopathy (CTE) due to a buildup of a specific protein in the brain.

But a new Northwestern Medicine study of 174 donated brains, including some from former high school and college football players, pumps the brakes on that theory. 

“The long and short of it is no, this protein in this specific brain region is not increased in people who played football at the amateur level. It throws a little bit of cold water on the current CTE narrative,” said corresponding author Dr. Rudolph Castellani, professor of pathology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine neuropathologist. 

The study was recently published in the Journal of Alzheimer’s Disease.

It raises important questions about how scientists interpret subtle brain changes associated with aging, Alzheimer’s disease and repetitive head impacts.

How the study worked

The study analyzed brain tissue from the Lieber Institute for Brain Development, which collects brain donations from people who had psychiatric conditions (e.g. schizophrenia, major depression, general anxiety, substance use disorder, etc.) throughout their life.

Of the 174 samples collected from older adult men (with a median age of 65 at death), 48 men participated in football in high school or college while 126 had no history of playing a contact or collision sport. 

The study did not include brains from professional athletes. 

The scientists focused on a small memory-related brain region called CA2, part of the hippocampus. This region has been shown to accumulate phosphorylated tau (p-tau) protein — which is often present in neurodegenerative disease — in a variety of contexts, including normal aging, Alzheimer’s disease and in individuals with a history of repetitive head impacts.

But the findings suggest p-tau buildup in CA2 isn’t specific to contact sports. The scientists found no over-representation of CA2 p-tau in individuals with a history of youth football participation. Instead, the presence of p-tau in this region was statistically associated with age.

“What’s novel here is a return to the null hypothesis — that there may be no link between repeated head injuries and p-tau buildup in this location,” said Castellani, who also is the neuropathology core director of the Northwestern University Alzheimer’s Disease Research Center.

“Rather than assuming p-tau in CA2 is inherently pathological, we’re asking whether it might be part of normal aging or a non-specific response to environmental factors.”

The study also highlights broader challenges in the field of neurodegeneration research. In particular, the authors point to the difficulty of assigning clinical meaning to subtle pathological findings.

The paper’s section, “Knowledge gaps and implications for future research,” underscores how even expert consensus groups struggle to define CTE in clinically meaningful terms.

“Modern studies on CTE may be expanding the boundaries of what’s considered normal variability in the human brain,” Castellani said. “This work reminds us to be cautious in interpreting pathology without clear clinical correlation.”

The authors call for larger studies to better understand how p-tau relates to aging and head injuries, while urging the scientific community to critically evaluate assumptions about what constitutes neurodegenerative disease.

About this CTE and neurology research news

Author: Kristin Samuelson
Source: Northwestern University
Contact: Kristin Samuelson – Northwestern University
Image: The image is credited to Neuroscience News

Original Research: Closed access.
“Postmortem tau in the CA2 region of the hippocampus in older adult men who participated in youth amateur American-style football” by Rudolph Castellani et al. Journal of Alzheimer’s Disease

Abstract

Postmortem tau in the CA2 region of the hippocampus in older adult men who participated in youth amateur American-style football

Background

Researchers have reported that hyperphosphorylated tau (p-tau) accumulates in the Cornu Ammonis 2 subfield (CA2) of the hippocampus with age, preferentially in primary age-related tau astrogliopathy, in association with early Alzheimer’s disease, and preferentially in chronic traumatic encephalopathy neuropathologic change.

Objective

Examine the possible association between preferential p-tau in the CA2 region of the hippocampus and history of playing high school American-style football.

Methods

Postmortem brain tissue samples were obtained from the Lieber Institute for Brain Development for 174 men (median age at death = 65 years; range = 50–96). There were 126 with no known history of participation in contact or collision sports and 48 (27.6%) who participated in football.

Results

Approximately half were rated modified Braak stage I (47.1%) and modified CERAD stage 0 (52.0%). Preferential CA2 p-tau was present in 29.9%. The average age for those with versus without preferential CA2 p-tau was 75 and 63, respectively (Cohen’s d = −1.27, large effect).

The sport history groups did not differ in age (p = 0.607). In both univariate and multivariate logistic regressions, older age groups (odds ratio [OR] = 3.42 and 3.23) and those with greater modified CERAD scores (OR = 1.78 and 1.48) were significantly more likely to have preferential CA2 p-tau. There was not a significant association between football participation and preferential CA2 p-tau.

Conclusions

There was not a significant association between participation in high school football and preferential CA2 p-tau identified after death. These results support other theories in the literature—that preferential CA2 p-tau is associated with aging and with Alzheimer’s disease neuropathologic change.