Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

Alzheimer disease

Solanezumab—prospects for meaningful interventions in AD?

A treatment trial of the monoclonal anti-amyloid antibody solanezumab showed slight benefits in people with dementia due to mild Alzheimer disease. Drug effects on several neuropsychological testing outcomes were statistically significant, but the effect sizes were unlikely to manifest as meaningful functional benefits. Here, we discuss the implications and possible molecular underpinnings.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

References

  1. Siemers, E. R. et al. Phase 3 solanezumab trials: secondary outcomes in mild Alzheimer's disease patients. Alzheimers Dement. http://dx.doi.org/10.1016/j.jalz.2015.06.1893.

  2. Liu, E. et al. Amyloid-β 11C-PiB-PET imaging results from 2 randomized bapineuzumab phase 3 AD trials. Neurology 85, 692–700 (2015).

    Article  CAS  Google Scholar 

  3. Jansen, W. J. et al. Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA 313, 1924–1938 (2015).

    Article  Google Scholar 

  4. Jack, C. R. Jr et al. Amyloid-first and neurodegeneration-first profiles characterize incident amyloid PET positivity. Neurology 81, 1732–1740 (2013).

    Article  CAS  Google Scholar 

  5. Lambert, M. P. et al. Diffusible, nonfibrillar ligands derived from Aβ1–42 are potent central nervous system neurotoxins. Proc. Natl Acad. Sci. USA 95, 6448–6453 (1998).

    Article  CAS  Google Scholar 

  6. Schöll, M. et al. Low PiB PET retention in presence of pathologic CSF biomarkers in Arctic APP mutation carriers. Neurology 79, 229–236 (2012).

    Article  Google Scholar 

  7. Lim, Y. Y. et al. Effect of amyloid on memory and decline from preclinical to clinical Alzheimer's disease. Brain 137, 221–231 (2014).

    Article  Google Scholar 

  8. Ramanan, V. K. et al. GWAS of longitudinal amyloid accumulation on 18F-florbetapir PET in Alzheimer's disease implicates microglial activation gene IL1RAP. Brain http://dx.doi.org/10.1093/brain/awv231.

  9. Lambert, J.-C. et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nat. Genet. 45, 1452–1458 (2013).

    Article  CAS  Google Scholar 

  10. Sperling, R. A. et al. The A4 study: stopping AD before symptoms begin? Sci. Transl. Med. 6, 228fs13 (2014).

    Article  Google Scholar 

Download references

Acknowledgements

The authors acknowledge NIH grants P50 AG005138 (to M.S.), and U01 AG046170, R34 AG049649, R01 NS075685, R21 AT005510, RF1 AG042965, VA MERIT Review Grant I01 RX000684, the Cure Alzheimer's Fund, and gifts from the Louis B. Mayer Foundation, the Sarah and Gideon Gartner Trust, the Rudin Foundation, and the Werber Family Foundation (to S.G.).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sam Gandy.

Ethics declarations

Competing interests

Within the past 5 years, S.G. has provided consultation to the Janssen Pfizer Immunotherapy Alliance and has held grants from Baxter, Amicus and Constellation/Polyphenolics. M.S. has provided consultation to Janssen Pharmaceuticals, Eli Lilly, Eisai, Medivation, Sanofi Aventis, Biogen and Takeda. She has also consulted for Merck and Nutricia without any compensation.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gandy, S., Sano, M. Solanezumab—prospects for meaningful interventions in AD?. Nat Rev Neurol 11, 669–670 (2015). https://doi.org/10.1038/nrneurol.2015.218

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneurol.2015.218

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing