Identification and validation of novel CSF biomarkers for early stages of Alzheimer's disease

Yan Hu, Ava Hosseini, John S.K. Kauwe, Julia Gross, Nigel J. Cairns, Alison M. Goate, Anne M. Fagan, R. Reid Townsend, David M. Holtzman

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


The pathology of Alzheimer's disease (AD) begins years prior to clinical diagnosis. The development of antecedent biomarkers that indicate the presence of AD pathology and predict risk for decline in both cognitively normal and mildly impaired individuals will be useful as effective therapies are developed. While cerebrospinal fluid (CSF) markers such as amyloid-β (Aβ) 42 and tau are useful, additional biomarkers are needed. To identify new markers, we utilized 2-D difference gel electrophoresis (2-D DIGE) of individual CSF samples from subjects with very mild AD versus controls after depletion of high-abundant proteins. Protein spots displaying differential abundance between the two groups were identified with MS. A number of candidate biomarkers were identified in 18 gel features. Selected candidates were quantified in a larger clinical set using ELISA. The mean levels of α1-antichymotrypsin (ACT), antithrombin III (ATIII), and zinc-α2-glycoprotein (ZAG) were significantly higher in the mild AD group, and the mean level of carnosinase 1 (CNDP1) was decreased. When these biomarkers are optimally combined, there is a strong trend toward greater specificity and sensitivity based on clinical diagnosis than when used individually. Our findings provide novel biomarker candidates for very mild and mild AD that can be further assessed as antecedent markers and predictors of clinical progression.

Original languageEnglish
Pages (from-to)1373-1384
Number of pages12
JournalProteomics - Clinical Applications
Issue number11
StatePublished - Nov 2007
Externally publishedYes


  • 2-D DIGE
  • Alzheimer's disease
  • Biomarker
  • Cerebrospinal fluid


Dive into the research topics of 'Identification and validation of novel CSF biomarkers for early stages of Alzheimer's disease'. Together they form a unique fingerprint.

Cite this