FTIR Spectroscopy of Cerebrospinal Fluid Reveals Variations in the Lipid: Protein Ratio at Different Stages of Alzheimer's Disease

J Alzheimers Dis. 2019;68(1):281-293. doi: 10.3233/JAD-181008.

Abstract

Alzheimer's disease (AD) is a disease of advanced civilization and a common form of dementia in people over 65 years of age. We used Fourier transform infrared (FTIR) spectroscopy combined with principal component analysis (PCA) to determine changes in the quantity and quality of the cerebrospinal fluid from AD patients at three different stages of the disease (ADI, ADII, and ADIII), as well as from patients with mild cognitive impairment (MCI). Moreover, based on the FTIR spectra, we calculated the ratio of α-helix and β-sheet secondary protein structures as well as the lipid-protein balance as potential AD markers. The FTIR spectra of cerebrospinal fluid obtained from MCI, ADI, ADII, and ADIII patients showed that peaks corresponding to protein and deoxyribonucleic acid (DNA), and phospholipid and lipid vibrations were shifted in comparison with those of control subjects. Furthermore, the levels of these chemical compounds were lower in the patients than in the control subjects. The β-sheet secondary protein structure levels were increased in the MCI and AD patients compared with the control subjects. In addition, significant changes in the lipid-protein balance were observed. Interestingly, as the disease progressed, the lipid-protein balance became further disrupted, that is, the lipid amount decreased with disease progression. PCA analysis of lipid-protein FTIR regions revealed that the spectra could be used to distinguish between controls and patients with MCI, ADI, ADII, and ADIII.

Keywords: Alzheimer’s disease; Fourier transform infrared spectroscopy; PCA-LDA; cerebrospinal fluid; lipid-protein balance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid*
  • Biomarkers / cerebrospinal fluid
  • Cerebrospinal Fluid Proteins / analysis*
  • Disease Progression
  • Female
  • Humans
  • Lipids / cerebrospinal fluid*
  • Male
  • Middle Aged
  • Spectroscopy, Fourier Transform Infrared

Substances

  • Biomarkers
  • Cerebrospinal Fluid Proteins
  • Lipids