Plasma biomarkers for mild cognitive impairment and Alzheimer's disease

Brain Res Rev. 2009 Oct;61(2):69-80. doi: 10.1016/j.brainresrev.2009.05.003. Epub 2009 May 21.


Purpose of review: With the move toward development of disease modifying treatments, there is a need for more specific diagnosis of early Alzheimer's disease (AD) and mild cognitive impairment (MCI), plasma biomarkers are likely to play an important role in this. We review the current state of knowledge on plasma biomarkers for MCI and AD, including unbiased proteomics and very recent longitudinal studies.

Recent findings: With the use of proteomics methodologies, some proteins have been identified as potential biomarkers in plasma and serum of AD patients, including alpha-1-antitrypsin, complement factor H, alpha-2-macroglobulin, apolipoprotein J, apolipoprotein A-I. The findings of cross-sectional studies of plasma amyloid beta (A beta) levels are conflicting, but some recent longitudinal studies have shown that low plasma A beta 1-42 or A beta 1-40 levels, or A beta 1-42/A beta 1-40 ratio may be markers of cognitive decline. Other potential biomarkers for MCI and AD reflecting a variety of pathophysiological processes have been assessed, including isoprostanes and homocysteine (oxidative stress), total cholesterol and ApoE4 allele (lipoprotein metabolism), and cytokines and acute phase proteins (inflammation). A panel of 18 signal proteins was reported as markers of MCI and AD.

Summary: A variety of potential plasma biomarkers for AD and MCI have been identified, however the findings need replication in longitudinal studies. This area of research promises to yield interesting results in the near future.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / blood*
  • Alzheimer Disease / diagnosis
  • Amyloid beta-Peptides / blood*
  • Biomarkers / blood
  • Cognition Disorders / blood*
  • Cognition Disorders / diagnosis
  • Humans
  • Lipoproteins / blood*
  • Oxidative Stress
  • Proteomics


  • Amyloid beta-Peptides
  • Biomarkers
  • Lipoproteins