An optimistic view for quantifying mRNA in post-mortem human brain

Brain Res Mol Brain Res. 2003 Aug 19;116(1-2):7-16. doi: 10.1016/s0169-328x(03)00208-0.

Abstract

Quantitative human mRNA data are derived from post-mortem or biopsied tissue. RNA degradation, poor replication, a large mRNA variance and confounding factors such as brain pH and age of death are often cited, however, as objections to the data's reliability. A central question is whether post-mortem human mRNA can be treated as a statistically ordered system. TaqMan real-time RT-PCR was used to measure seven mRNAs in 513 cortical samples taken from 90 Alzheimer's disease and 81 control brains. Despite a high mRNA variance strong correlations were found between the mRNA transcripts in a single brain. Where a brain has a high/low level of one mRNA, the same brain invariably has a high/low level of other mRNAs; correlated order is present and allows removal of that source of variation common to all genes. Although levels of mRNA are highly variable between subjects (>1000-fold), quantitative order is present in post-mortem human mRNA, allowing effects due to pathology or gender to be isolated and tested for significance.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Brain Chemistry*
  • Cadaver
  • Case-Control Studies
  • Female
  • Glial Fibrillary Acidic Protein / genetics
  • Glyceraldehyde-3-Phosphate Dehydrogenases / genetics
  • Humans
  • Linear Models
  • Male
  • Microtubule-Associated Proteins / genetics
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Peptide Fragments / genetics
  • Postmortem Changes
  • RNA Stability
  • RNA, Messenger / analysis*
  • RNA, Messenger / chemistry
  • Reproducibility of Results
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Sex Factors
  • Taq Polymerase

Substances

  • Amyloid beta-Protein Precursor
  • Glial Fibrillary Acidic Protein
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Peptide Fragments
  • RNA, Messenger
  • amyloid beta-protein precursor 770 (301-323)
  • Glyceraldehyde-3-Phosphate Dehydrogenases
  • Taq Polymerase