Amyloid removal may reduce tau buildup and neurodegeneration in Alzheimer’s disease
In a brain autopsy of a Penn Medicine clinical trial participant, regions cleared of amyloid showed little tau buildup, while nearby areas with persistent amyloid had greater signs of damage.
2 min. read
An analysis of the brain of a deceased Alzheimer’s disease (AD) clinical trial participant at Penn Medicine has found that regions where an anti-amyloid therapy successfully cleared amyloid plaques show little to no evidence of tau tangles, a hallmark of AD closely linked to neurodegeneration and cognitive decline. In contrast, neighboring areas where amyloid remains show substantially more tau pathology and signs of ongoing brain damage.
Kateryna Kon/Science Photo Library via Getty Images
The findings provide rare human evidence that clearing amyloid plaques may have long-term effects on the biological processes that drive AD. The study also suggests that removing amyloid early and extensively may slow the progression of the disease by limiting the accumulation of tau and subsequent neurodegeneration, according to findings presented at the 2026 Alzheimer’s Association International Conference by researchers from the Perelman School of Medicine, and published in JAMA.
“Seeing both disease patterns side-by-side in the same brain gave us a rare opportunity to understand how amyloid removal affects other proteins that contribute to Alzheimer’s disease,” says co-senior author David Wolk, co-director of the Penn Memory Center, and director of the Penn Alzheimer’s Disease Research Center. “The findings provide some of the clearest human evidence to date that anti-amyloid therapies may limit the accumulation of tau and slow the brain changes that lead to memory loss and cognitive decline.”
Scientists have long suspected that amyloid accumulation enables tau tangles to take hold. However, opportunities to directly examine how amyloid removal affects tau are rare because relatively few patients who have received anti-amyloid therapies have come to autopsy.
This report analyzed the brain of a man in his fifties, diagnosed with mild cognitive impairment due to AD, who enrolled in a clinical trial of aducanumab and received 30 doses over four and a half years. When neuropathologists examined the brain, they found an unusual patchwork pattern.
Areas called gyri, the crests of the brain’s folds, were largely cleared of amyloid plaques and showed minimal tau accumulation. Nearby sulci, the grooves between those folds, retained substantial amyloid and displayed much greater tau accumulation, inflammation, and neurodegeneration. The pattern closely matched brain imaging collected during the participant’s life, which had shown uneven amyloid clearance across different regions of the brain.
When the Schuylkill swallowed the city: Lessons from Hurricane Ida’s historic flood
New Penn research shows that Hurricane Ida wasn’t a once-in-a-century anomaly but a preview of how climate change, urbanization, and aging infrastructure are rewriting flood risk.
The Fed explained: What it does and why it matters
Former Philadelphia Fed President Patrick Harker and financial historian Peter Conti-Brown, both Wharton professors, unpack the central bank’s origins, its unusual structure, and the quiet ways it shapes the economy
How population changes are impacting primary education worldwide
Research from Penn sociologist Emily Hannum and colleagues reveals regional trends in whether school-age populations are increasing, plateauing, or decreasing—and shows how different countries are responding.
A bioengineered bean gum from the lab of Penn Dental’s Henry Daniell is found to reduce the levels of three microbes associated with head and neck squamous cell cancer to almost zero, without affecting the beneficial bacteria normally found in the mouth.
Fighting oral cancer with bioengineered chewing gum
Research led by Penn Dental’s Henry Daniell shows that antiviral and antibacterial chewing gums reduce the levels of three microbes linked to worse outcomes in oral cancers, paving the way for more effective and affordable therapies.
