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Alzheimer disease and aducanumab: adjusting our approach

Nature Reviews Neurology volume 15, pages 365–366 (2019)Cite this article

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In the march towards disease-modifying treatments for Alzheimer disease, immunotherapy with antibodies against amyloid-β protein is furthest along in human trials. The news that Biogen’s aducanumab showed no cognitive benefit in phase III trials requires careful analysis of what went wrong and how to position anti-amyloid agents among other therapeutic approaches.

The looming personal and societal tragedy of Alzheimer disease (AD) has motivated an accelerating global effort to understand and treat this complex disorder of ageing. Beginning in the early 1980s, studies of the biochemistry, neuropathology, genetics and biomarker alterations associated with AD have led to numerous clinical trials aimed at identifying therapeutics that can slow the rate of cognitive decline. Symptomatic treatments that provide temporary benefit emerged early on, but the development of truly disease-modifying drugs for AD has not yet been achieved. In March, an interim analysis by Biogen of their late (phase III) trials of aducanumab, a monoclonal antibody targeting oligomers and fibrils of the amyloid-β (Aβ) protein, revealed no significant slowing of cognitive decline in patients with mildly symptomatic AD. This is a great disappointment for our patients and for the field of AD therapeutic development.

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  1. Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Dennis J. Selkoe

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  1. Dennis J. Selkoe
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Correspondence to Dennis J. Selkoe.

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D.J.S. is a consultant for E-Scape Bio and Prothena.

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Selkoe, D.J. Alzheimer disease and aducanumab: adjusting our approach. Nat Rev Neurol 15, 365–366 (2019). https://doi.org/10.1038/s41582-019-0205-1

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