Evidence map›Paper›PMID 40760501›Full record

ArticleAlzheimer's research & therapy2025

Aducanumab binds high molecular weight soluble Aβ oligomers and restores intracellular calcium levels.

Lu Yu, Xueying Wang, Tri H Doan, Yutian Fan, Thierry Bussiere, Brian J Bacskai, Ksenia V Kastanenka

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Article in Alzheimer's research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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0cells of the map it votes in
2citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Lu Yu *Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown Boston, MA, 02129, USA.
Xueying Wang *Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown Boston, MA, 02129, USA.
Tri H DoanDepartment of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown Boston, MA, 02129, USA.
Yutian FanBrandeis University, Waltham, MA, 02453, USA.
Thierry BussiereBiogen, Inc., Cambridge, MA, 02142, USA.
Brian J BacskaiDepartment of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown Boston, MA, 02129, USA.
Ksenia V KastanenkaDepartment of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown Boston, MA, 02129, USA. kkastanenka@mgh.harvard.edu.

Funding

Elucidating circuit disruptions in Alzheimer's diseaseR01AG066171 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI KASTANENKA, KSENIA V. · 2020 to 2024
$2.9M
Advanced Program of The Affiliated Hospital of Xuzhou Medical University PYJH2024314NIA NIH HHS R01 AG066171
6 · The paper itself

Abstract

backgroundAlzheimer's disease (AD) is characterized by amyloid-beta (Aβ) accumulation, leading to the formation of neurotoxic soluble oligomers (AβOs) that impair calcium homeostasis in neurons and astrocytes. Aducanumab, a fully human monoclonal antibody targeting aggregated Aβ, has been approved for AD treatment due to its ability to reduce amyloid plaque burden. However, its specificity toward different AβO species and its functional impact on calcium homeostasis remain unclear.

methodsWe investigated aducanumab's ability to recognize and immunodeplete low-molecular-weight (LMW) and high-molecular-weight (HMW) AβOs using three Aβ preparations: (1) transgenic conditioned media (TgCM) from cultured Tg2576 neurons, (2) synthetic Aβ42-derived diffusible ligands (ADDLs), and (3) TBS-soluble fractions from aged Tg2576 mouse brain. Size exclusion chromatography and ELISA were used to characterize AβO species. Multiphoton calcium imaging of neuron-astrocyte co-cultures was performed to assess the impact of aducanumab on AβO-induced calcium overload.

resultsAducanumab preferentially bound and immunodepleted HMW AβOs in ADDLs and the TBS-soluble fraction of Tg2576 mouse brain extracts but did not recognize LMW AβOs in TgCM. In calcium imaging experiments, all three AβO preparations induced calcium overload in neuron-astrocyte co-cultures. Immunodepletion with aducanumab prevented calcium overload in cultures exposed to ADDLs and Tg2576 brain extracts but not in those treated with immunodepleted TgCM, indicating that aducanumab selectively neutralizes HMW AβOs.

conclusionsOur findings demonstrate that aducanumab specifically targets HMW AβOs, mitigating their neurotoxic effects by restoring intracellular calcium homeostasis. These results provide mechanistic insight into aducanumab's therapeutic action and support its potential role in modifying AD pathology by selectively neutralizing Aβ species.

Indexed as

Amyloid beta-PeptidesAntibodies, Monoclonal, HumanizedCalciumPeptide FragmentsAlzheimer DiseaseAnimalsAstrocytesBrainCells, CulturedCoculture TechniquesHumansMiceMice, TransgenicMolecular WeightNeuronsaducanumabAmyloid beta-Peptidesamyloid beta-protein (1-42)Antibodies, Monoclonal, HumanizedCalciumPeptide Fragments

Identifiers

PMID40760501
PMCPMC12323110

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.