Advances in multiplex PCR for Alzheimer's disease diagnostics targeting CDK genes

Neurosci Lett. 2021 Apr 1:749:135715. doi: 10.1016/j.neulet.2021.135715. Epub 2021 Feb 15.

Abstract

Alzheimer's disease (AD) is a common neurodegenerative disease that lacks biomarkers for diagnosis. Biomarkers for accurate detection of AD are required for potential therapeutic approaches. Recent studies in mammalian cells have demonstrated an association between the expression of cell cycle proteins and AD occurrence. Therefore, we aimed to identify a potent biomarker among relevant cell cycle-regulating proteins such as cyclin-dependent kinases (CDKs) for the diagnosis of AD. We also developed a multiplex-PCR-based diagnostic method, which showed the rapid and accurate detection of AD biomarkers. Genome-wide association study (GWAS) results showed increased gene expression of CDKs in an AD mouse model. Based on genomic analysis, our multiplex-PCR method, which contained optimized primer sets and PCR conditions targeting genes of CDKs, accurately matched RT-PCR results in the AD mouse model. Interestingly, validation by in silico meta-analysis for the expression of each CDK gene showed significant expression in moderate and severe groups of AD patients. Accordingly, clinical applications relying on the diagnosis of AD using our results may shed light on AD therapeutics.

Keywords: Alzheimer’s disease; Biomarker; CDKs; Diagnosis; GWAS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Animals
  • Biomarkers / metabolism*
  • Cell Cycle / genetics
  • Cell Cycle / physiology
  • Cyclin-Dependent Kinases / genetics*
  • Cyclin-Dependent Kinases / metabolism
  • Disease Models, Animal
  • Genome-Wide Association Study
  • Humans
  • Mice
  • Multiplex Polymerase Chain Reaction / methods
  • Neurodegenerative Diseases / diagnosis
  • Neurodegenerative Diseases / genetics*

Substances

  • Biomarkers
  • Cyclin-Dependent Kinases