How Autopsy Research Is Shaping Understanding of Anti-Amyloid Therapies Edward B. Lee, MD, PhD

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“Postmortem and longitudinal imaging findings provide new insights into the potential downstream effects of amyloid clearance on tau pathology and neurodegeneration in Alzheimer disease.”

As amyloid-targeting therapies become increasingly integrated into Alzheimer disease (AD) care, questions remain about their long-term effects on the underlying biology of the disease and whether amyloid clearance may influence downstream pathology. To better understand these potential effects, investigators conducted a clinicopathologic case report examining a man in his 50s with mild cognitive impairment due to AD who carried the p.R47H TREM2 variant and received aducanumab, a formerly approved drug for AD, as part of the EMERGE clinical trial and subsequent EMBARK open-label extension.

The patient received 30 doses of aducanumab over 4.5 years and underwent longitudinal clinical assessments, amyloid and tau PET imaging, and serial MRI. After his death approximately 4 years after his final dose, investigators conducted an extensive neuropathologic examination of his brain and compared the findings with those from 14 untreated individuals with AD matched by age and/or TREM2 variant. By integrating postmortem pathology with longitudinal in vivo imaging, researchers evaluated the relationship between amyloid clearance and downstream AD pathology and neurodegeneration.

The findings were presented at the 2026 Alzheimer’s Association International Conference (AAIC), held July 12-15 in London, United Kingdom, and offered new clinicopathologic insights into the long-term effects of amyloid-targeting therapy as well as the relationship between amyloid clearance and downstream Alzheimer disease pathology. To gain a deeper understanding of what the results mean for clinicians, NeurologyLive® spoke with the study’s senior author, Edward B. Lee, MD, PhD, Trojanowski Professor for Neurodegenerative Disease Research at the University of Pennsylvania.

Throughout the interview, Lee discussed the neuropathologic findings observed in a patient who received anti-amyloid therapy. He also addressed the importance of autopsy research in understanding the long-term biological effects of emerging AD therapies, noting the unique insights that postmortem analyses can provide beyond biomarkers and imaging. Furthermore, Lee discussed the need for continued investment in brain donation, longitudinal research, and research infrastructure to further evaluate the effects of anti-amyloid therapies and identify new discoveries in AD.

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