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Northwestern scientists studied 174 brain samples. CTE and aging were difficult to distinguish

Findings show the brain protein tied to CTE is not elevated in former amateur football players
CTE
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. Getty Images

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

Where did these brain samples come from?

The study, published in the Journal of Alzheimer’s Disease, examined brain tissue from the Lieber Institute for Brain Development, which collects brain donations from people who had psychiatric conditions — 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.

Focus was on a small, memory-related brain region

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.

Is this just part of normal aging?

Interestingly, 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, underscoring how even expert consensus groups struggle to define CTE in clinically meaningful terms.

So, what accounts for disease?

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.

“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.”