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Immunotherapy with Aducanumab restores calcium homeostasis in Tg2576 mice


Year of Publication:
Contact PI Name:
Brian J. Bacskai
Contact PI Affiliation:
Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Massachusetts, USA
Ksenia V. Kastanenka, Thierry Bussiere, Naomi Shakerdge, Fang Qian, XPaul H. Weinreb, Ken Rhodes
Primary Reference (PubMED ID):
Funding Source:
Alzheimer's Association
National Institutes of Health (NIH)
Study Goal and Principal Findings:

Calcium homeostasis plays a major role in maintaining neuronal function under physiological conditions. Amyloid-β (Aβ) initiates pathological processes that include disruption in intracellular calcium levels, so amelioration of the calcium alteration could serve as an indirect functional indicator of treatment efficacy. Therefore, calcium dynamics were used as a measure of functional outcome. This study evaluated the effects of the anti-Aβ antibody aducanumab on calcium homeostasis and plaque clearance in aged Tg2576 mice with in vivo multiphoton imaging. Acute topical application of aducanumab to the brain resulted in clearance of amyloid plaques. Although chronic systemic administration of aducanumab in 22-month-old mice did not clear existing plaques, calcium overload was ameliorated over time. Therefore, this antibody likely restores neuronal network function that possibly underlies cognitive deficits, indicating promise as a clinical treatment. In addition, functional readouts such as calcium overload may be a more useful outcome measure to monitor treatment efficacy in models of Alzheimer’s disease compared with amyloid burden alone.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Immunotherapy(passive)
Therapeutic Agent:
Therapeutic Target:
beta Amyloid Peptide

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
Not Reported

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest


Outcome Measured
Outcome Parameters
beta Amyloid Load
beta Amyloid Deposits
Dense-core/Compact Plaques
Cerebral Amyloid Angiopathy (CAA)
Glutamate Ionotropic Receptor NMDA Type Subunit 2B (GluN2B/NR2B)
Glutamate Ionotropic Receptor NMDA Type Subunit 2A (GluN2A/NR2A)
Ryanodine Receptor (RyR)
Sarco/Endoplasmic Reticulum Ca²⁺-ATPase (SERCA)
Visinin-Like Protein 1 (VILIP1)
Inositol Trisphosphate Receptor (IP3R)
Glutamate Ionotropic Receptor NMDA Type Subunit 1 (GRIN1/NR1)
In Vivo Two-Photon Calcium Imaging
In Vivo Two-Photon Amyloid Imaging
Cell Biology
Intracellular Calcium Concentration
Antibody Concentration-Brain
Target Engagement (Reduction beta Amyloid Peptides-Brain)
Target Engagement (Binding beta Amyloid Antibodies to beta Amyloid Deposits)