Alzheimer's Disease Is Responsible for Progressive Age-Dependent Differential Expression of Various Protein Cascades in Retina of Mice

ACS Chem Neurosci. 2019 May 15;10(5):2418-2433. doi: 10.1021/acschemneuro.8b00710. Epub 2019 Feb 13.

Abstract

Alzheimer's disease (AD) is a devastating neurodegenerative disease associated with cognitive impairments and memory loss usually in aged people. In the past few years, it has been detected in the eye retina, manifesting the systematic spread of the disease. This might be used for biomarker discovery for early detection and treatment of the disease. Here, we have described the proteomic alterations in retina of 2, 4, and 6 months old 3×Tg-AD mice by using iTRAQ (isobaric tags for relative and absolute quantification) proteomics technology. Out of the total identified proteins, 121 (71 up- and 50 down-regulated), 79 (51 up- and 28 down-regulated), and 153 (37 up- and 116 down-regulated) significantly differentially expressed proteins (DEPs) are found in 2, 4, and 6 month's mice retina (2, 4, and 6 M), respectively. Seventeen DEPs are found common in these three groups with consistent expression behavior or opposite expression in the three groups. Bioinformatics analysis of these DEPs highlighted their involvement in vital AD-related biological phenomenon. To further prompt the results, four proteins from 2 M group, three from 4 M, and four from 6 M age groups are successfully validated with Western blot analysis. This study confirms the retinal involvement of AD in the form of proteomic differences and further explains the protein-based molecular mechanisms, which might be a step toward biomarker discovery for early detection and treatment of the disease.

Keywords: Alzheimer’s disease; aging; biomarker discovery; iTRAQ proteomics; retina.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Alzheimer Disease / metabolism*
  • Animals
  • Biomarkers / metabolism
  • Computational Biology
  • Down-Regulation / physiology
  • Eye Proteins / metabolism*
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Proteomics
  • Retina / metabolism*
  • Up-Regulation / physiology

Substances

  • Biomarkers
  • Eye Proteins