Neuropathological study of the effects of aducanumab anti-Aβ immunotherapy on patients with Alzheimer’s disease
13 affiliations
- 1Department of Neurology, Massachusetts General Hospital, Charlestown, MA, 02129, USA
- 2Harvard Medical School, Boston, MA, 02115, USA
- 3Department of Pathology, C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Boston, MA, 02115, USA
- 4Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA
- 5Headlands Research Eastern MA, Plymouth, MA, 02360, USA
- 6Warren Alpert Medical School of Brown University, Providence, RI, 02906, USA
- 7Cleveland Clinic Lou Ruvo Center for Brain Health - Las Vegas, Las Vegas, NV, 89106, USA
- 8Kingfisher Cooperative, LLC, Spokane, WA, 99201, USA
- 9Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98115, USA
- 10Biogen, 225 Binney Street, Cambridge, MA, 02142, USA
- 11University of California San Diego, La Jolla, CA, 92093, USA
- 12Department of Neurology, Massachusetts General Hospital, Charlestown, MA, 02129, USA. [email protected]
- 13Harvard Medical School, Boston, MA, 02115, USA. [email protected]
Abstract
Fluid and imaging biomarker data show that anti-amyloid (Aβ) antibodies promote the clearance of Aβ from the brains of patients with Alzheimer’s disease (AD). We examined postmortem brain tissue of individuals who participated in aducanumab clinical trials and investigated the drug’s effects on Aβ pathology and other AD phenotypes. The medial temporal lobe of six aducanumab clinical trial participants—who had extensive exposure to aducanumab and happened to die between 7 weeks and 5 years after their last antibody infusion—was compared with that of nine untreated AD patients matched for age, APOE genotype, and Braak neurofibrillary tangle stage, to determine how aducanumab impacts AD pathobiology. Patients treated with aducanumab displayed a robust reduction in Aβ burden. As observed in previous studies, Aβ was associated with non-arterial microvessels in aducanumab-treated patients, suggesting a redistribution of Aβ within the neuropil. Neuritic phospho-tau decreased in parallel with fewer Aβ plaques, but the density of PHF-1 + and AT8 + neurofibrillary tangles remained unchanged relative to the average untreated AD donor. Measures of microglial and astroglial reactivity were also comparable to those in untreated AD controls. These findings confirm aducanumab’s potent ability to target and remove brain Aβ. On average, Aβ plaques increased in proportion to the length of time after the last dose, consistent with the idea that plaques gradually redeposit post-treatment. The selective reduction of neuritic, but not neurofibrillary tangle phospho-tau implies that Aβ-targeted antibodies such as aducanumab alleviate plaque-associated dystrophy but may not address established tangles. This study describes the long-term outcomes of anti-Aβ immunotherapy in AD.
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BibTeX
@article{welikovitch2026neuropathological,
title = {{Neuropathological study of the effects of aducanumab anti-Aβ immunotherapy on patients with Alzheimer’s disease}},
author = {Lindsay A. Welikovitch and Derek H. Oakley and Rachel E. Bennett and Alberto Serrano‐Pozo and Haoyang Zhu and Nancy E. Ruiz‐Uribe and Theodore J. Zwang and Lori Beth Chibnik and Teresa Gómez‐Isla and Matthew P. Frosch and Donald S. Marks and Stephen Salloway and Charles B. Bernick and David R. Greeley and Caitlin S. Latimer and Amber Nolan and R. Matthew Hutchison and Carrie E. Rubel and Thierry Bussière and Edward D. Plowey and C. Dirk Keene and Bradley T. Hyman},
journal = {Acta Neuropathologica},
year = {2026},
month = jun,
doi = {10.1007/s00401-026-03037-y},
url = {https://doi.org/10.1007/s00401-026-03037-y},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Neuropathological study of the effects of aducanumab anti-Aβ immunotherapy on patients with Alzheimer’s disease
AU - Lindsay A. Welikovitch
AU - Derek H. Oakley
AU - Rachel E. Bennett
AU - Alberto Serrano‐Pozo
AU - Haoyang Zhu
AU - Nancy E. Ruiz‐Uribe
AU - Theodore J. Zwang
AU - Lori Beth Chibnik
AU - Teresa Gómez‐Isla
AU - Matthew P. Frosch
AU - Donald S. Marks
AU - Stephen Salloway
AU - Charles B. Bernick
AU - David R. Greeley
AU - Caitlin S. Latimer
AU - Amber Nolan
AU - R. Matthew Hutchison
AU - Carrie E. Rubel
AU - Thierry Bussière
AU - Edward D. Plowey
AU - C. Dirk Keene
AU - Bradley T. Hyman
PY - 2026
DA - 2026/06/16
JO - Acta Neuropathologica
DO - 10.1007/s00401-026-03037-y
UR - https://doi.org/10.1007/s00401-026-03037-y
AB - Fluid and imaging biomarker data show that anti-amyloid (Aβ) antibodies promote the clearance of Aβ from the brains of patients with Alzheimer’s disease (AD). We examined postmortem brain tissue of individuals who participated in aducanumab clinical trials and investigated the drug’s effects on Aβ pathology and other AD phenotypes. The medial temporal lobe of six aducanumab clinical trial participants—who had extensive exposure to aducanumab and happened to die between 7 weeks and 5 years after their last antibody infusion—was compared with that of nine untreated AD patients matched for age, APOE genotype, and Braak neurofibrillary tangle stage, to determine how aducanumab impacts AD pathobiology. Patients treated with aducanumab displayed a robust reduction in Aβ burden. As observed in previous studies, Aβ was associated with non-arterial microvessels in aducanumab-treated patients, suggesting a redistribution of Aβ within the neuropil. Neuritic phospho-tau decreased in parallel with fewer Aβ plaques, but the density of PHF-1 + and AT8 + neurofibrillary tangles remained unchanged relative to the average untreated AD donor. Measures of microglial and astroglial reactivity were also comparable to those in untreated AD controls. These findings confirm aducanumab’s potent ability to target and remove brain Aβ. On average, Aβ plaques increased in proportion to the length of time after the last dose, consistent with the idea that plaques gradually redeposit post-treatment. The selective reduction of neuritic, but not neurofibrillary tangle phospho-tau implies that Aβ-targeted antibodies such as aducanumab alleviate plaque-associated dystrophy but may not address established tangles. This study describes the long-term outcomes of anti-Aβ immunotherapy in AD.
SN - 0001-6322
SN - 1432-0533
ER -