• Ksenia V Kastanenka, Thierry Bussiere, Naomi Shakerdge, Fang Qian, Paul H Weinreb, Ken Rhodes, and Brian J Bacskai.
• Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Massachusetts 02129, and bbacskai@mgh.harvard.edu kkastanenka@mgh.harvard.edu.
• J. Neurosci. 2016 Dec 14; 36 (50): 12549-12558.

AbstractCalcium 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. We 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.Copyright © 2016 the authors 0270-6474/16/3612549-10$15.00/0.

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