Amyloid precursor protein mRNA levels in Alzheimer's disease brain

Brain Res Mol Brain Res. 2004 Mar 17;122(1):1-9. doi: 10.1016/j.molbrainres.2003.08.022.


Insoluble beta-amyloid deposits in Alzheimer's disease (AD) brain are proteolytically derived from the membrane bound amyloid precursor protein (APP). The APP gene is differentially spliced to produce isoforms that can be classified into those containing a Kunitz-type serine protease inhibitor domain (K(+), APP(751), APP(770), APRP(365) and APRP(563)), and those without (K(-), APP(695) and APP(714)). Given the hypothesis that Abeta is a result of aberrant catabolism of APP, differential expression of mRNA isoforms containing protease inhibitors might play an active role in the pathology of AD. We took 513 cerebral cortex samples from 90 AD and 81 control brains and quantified the mRNA isoforms of APP with TaqMan real-time RT-PCR. After adjustment for age at death, brain pH and gender we found a change in the ratio of KPI(+) to KPI(-) mRNA isoforms of APP. Three separate probes, designed to recognise only KPI(+) mRNA species, gave increases of between 28% and 50% in AD brains relative to controls (p=0.002). There was no change in the mRNA levels of KPI-(APP 695) (p=0.898). Therefore, whilst KPI-mRNA levels remained stable the KPI(+) species increased specifically in the AD brains.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Protein Precursor / classification
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism*
  • Analysis of Variance
  • Case-Control Studies
  • Cerebral Cortex / metabolism*
  • Female
  • Glial Fibrillary Acidic Protein / analysis
  • Glial Fibrillary Acidic Protein / genetics
  • Humans
  • Linear Models
  • Male
  • Microtubule-Associated Proteins / analysis
  • Microtubule-Associated Proteins / genetics
  • Middle Aged
  • Protein Isoforms / analysis
  • Protein Isoforms / classification
  • Protein Isoforms / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Sex Factors


  • Amyloid beta-Protein Precursor
  • Glial Fibrillary Acidic Protein
  • Microtubule-Associated Proteins
  • Protein Isoforms
  • RNA, Messenger