Multifactorial Analysis of a Biomarker Pool for Alzheimer Disease Risk in a North Indian Population

Dement Geriatr Cogn Disord. 2017;44(1-2):25-34. doi: 10.1159/000477206. Epub 2017 Jun 21.

Abstract

Background: Alzheimer disease (AD) is a progressive neurodegenerative disease with a complex multifactorial etiology. Here, we aim to identify a biomarker pool comprised of genetic variants and blood biomarkers as predictor of AD risk.

Methods: We performed a case-control study involving 108 cases and 159 non-demented healthy controls to examine the association of multiple biomarkers with AD risk.

Results: The APOE genotyping revealed that ε4 allele frequency was significantly high (p value = 0.0001, OR = 2.66, 95% CI 1.58-4.46) in AD as compared to controls, whereas ε2 (p = 0.0430, OR = 0.29, CI 0.07-1.10) was overrepresented in controls. In biochemical assays, significant differences in levels of total copper, free copper, zinc, copper/zinc ratio, iron, epidermal growth factor receptor (EGFR), leptin, and albumin were also observed. The AD risk score (ADRS) as a linear combination of 6 candidate markers involving age, education status, APOE ε4 allele, levels of iron, Cu/Zn ratio, and EGFR was created using stepwise linear discriminant analysis. The area under the ROC curve of the ADRS panel for predicting AD risk was significantly high (AUC = 0.84, p < 0.0001, 95% CI 0.78-0.89, sensitivity = 70.0%, specificity = 83.8%) compared to individual parameters.

Conclusion: These findings support the multifactorial etiology of AD and demonstrate the ability of a panel involving 6 biomarkers to discriminate AD cases from non-demented healthy controls.

Keywords: Alzheimer disease; Apolipoprotein E; Biomarker; Case-control study; Plasma; Serum.

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / blood
  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / epidemiology
  • Alzheimer Disease* / genetics
  • Apolipoprotein E4 / genetics*
  • Biomarkers / blood
  • Case-Control Studies
  • Causality
  • Copper / blood
  • Educational Status
  • ErbB Receptors / blood
  • Female
  • Gene Frequency
  • Humans
  • India / epidemiology
  • Iron / blood*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Risk Assessment / methods
  • Risk Factors
  • Zinc / blood

Substances

  • Apolipoprotein E4
  • Biomarkers
  • Copper
  • Iron
  • EGFR protein, human
  • ErbB Receptors
  • Zinc