Autopsy suggests Alzheimer's drug was less effective on deeper brain layers

Embargoed until: Publicly released: 2026-07-13 02:15

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An autopsy on a patient who received the Alzheimer's drug aducanumab (sold under the name Aduhelm) has shown better clearance of amyloid in the top layers of the brain compared to the deep layers. The drug was thought to work by removing beta-amyloid, one of the hallmarks of Alzheimer's disease, and it had accelerated approval in the US, but was discontinued in 2024. The autopsy showed the patient, who took the drug for 4.5 years, had greater clearance of amyloid from top layers of his brain compared to deep layers. The researchers also found higher levels of amyloid down in the folds of the brain (known as sulci) compared to up on the ridges (known as gyri). The authors say further research is needed to work out how amyloid can be cleared from these deeper layers because extensive clearance may be needed to see a benefit from these sorts of drugs.

News release

From: JAMA

Clinicopathologic Evaluation of Amyloid Clearance in Alzheimer Disease

About The Study: In this case report, areas of extensive amyloid clearance after amyloid-targeting therapy were associated with less downstream neuropathologic change. In addition, amyloid clearance appears to preferentially occur in the gyral crests. Future studies should evaluate the differential mechanisms involved in amyloid clearance from superficial and deep cortical layers and in gyri and sulci because extensive amyloid clearance may be necessary to achieve downstream neuropathologic benefit after removal of amyloid.

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conference: JAMA

Research:Paper

Organisation/s: University of Pennsylvania, USA

Funder: This work was supported by grants P30-AG072979, RF1-AG069474, R01-AG056014, R01-AG055005, R01-AG072796, R01-AG065341, P01-AG66597, and P01-AG084497 from the National Institutes of Health; by grant 2019NF4100087335 from the Pennsylvania Department of Health; by grant AACSF-23-1152241 from the Alzheimer’s Association and the Fred and Barbara Erb Family Foundation; support from the DeCrane Family Fund for PPA Research; and by gifts from the Shanahan Family Foundation and the Barrist Family Foundation.

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