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

Preclinical Alzheimer disease — the new frontier

Nature Reviews Neurology volume 12, pages 620–621 (2016)Cite this article

Subjects

Studies of preclinical Alzheimer disease (AD) have unexpectedly shown amyloid-β deposition and/or AD-like neurodegenerative changes in the brains of a high proportion of clinically normal elderly individuals. As two recent reports illustrate, imaging and fluid biomarker studies in these individuals are yielding new insights into the pathophysiology of cognitive ageing.

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

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

References

  1. Gordon, B. A. et al. Longitudinal β-amyloid deposition and hippocampal volume in preclinical Alzheimer disease and suspected non-Alzheimer disease pathophysiology. JAMA Neurol. http://dx.doi.org/10.1001/jamaneurol.2016.2642 (2016).

  2. Mormino, E. C. et al. Heterogeneity in suspected non-Alzheimer disease pathophysiology among clinically normal older individuals. JAMA Neurol. http://dx.doi.org/10.1001/jamaneurol.2016.2237 (2016).

  3. Jack, C. R. Jr et al. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol. 9, 119–128 (2010).

    Article  CAS  Google Scholar 

  4. Sperling, R. A. et al. Towards defining the preclinical stage of Alzheimer's disease: recommendations from the National Institute on Aging and the Alzheimer's Association Workgroup. Alzheimers Dement. 7, 280–292 (2011).

    PubMed  PubMed Central  Google Scholar 

  5. Jack, C. R. Jr et al. An operational approach to National Institute on Aging–Alzheimer's Association criteria for preclinical Alzheimer disease. Ann. Neurol. 71, 765–775 (2012).

    Article  Google Scholar 

  6. Jack, C. R. Jr et al. Suspected non-Alzheimer disease pathophysiology — concept and controversy. Nat. Rev. Neurol. 12, 117–124 (2016).

    Article  CAS  Google Scholar 

  7. Johnson, K. A. et al. Tau positron emission tomographic imaging in aging and early Alzheimer's disease. Ann. Neurol. 79, 110–119 (2016).

    Article  Google Scholar 

  8. Mormino, E. C. et al. Synergistic effect of β-amyloid and neurodegeneration on cognitive decline in clinically normal individuals. JAMA Neurol. 71, 1379–1385 (2014).

    Article  Google Scholar 

  9. Burnham, S. C. et al. Clinical and cognitive trajectories in cognitively healthy elderly individuals with suspected non-Alzheimer's disease pathophysiology (SNAP) or Alzheimer's disease pathology: a longitudinal study. Lancet Neurol. 15, 1044–1053 (2016).

    Article  Google Scholar 

  10. Boche, D., Denham, N., Holmes, C. & Nicoll, J. A. Neuropathology after active Aβ42 immunotherapy: implications for Alzheimer's disease pathogenesis. Acta Neuropathol. 120, 369–384 (2010).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The author gratefully acknowledges research supported from the NIH (grants P50 AG16574, U01 AG06786 R01 AG11378 and R01 AG41851), and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program of the Mayo Foundation.

Author information

Authors and Affiliations

  1. David S. Knopman is in the Department of Neurology, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.,

    David S. Knopman

Authors
  1. David S. Knopman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David S. Knopman.

Ethics declarations

Competing interests

The author serves on a Data Safety Monitoring Board for Lundbeck Pharmaceuticals and for the DIAN study, and is an investigator in clinical trials sponsored by Biogen, TauRX Pharmaceuticals, Lilly Pharmaceuticals and the Alzheimer's Disease Treatment and Research Institute, University of Southern California.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Knopman, D. Preclinical Alzheimer disease — the new frontier. Nat Rev Neurol 12, 620–621 (2016). https://doi.org/10.1038/nrneurol.2016.153

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneurol.2016.153

This article is cited by

Search

Advanced 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