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Amyloid precursor protein mRNA levels in Alzheimer's disease brain

Paul Preece1, David J Virley, Moheb Costandi

  • 1Seixo Branco, Departamento de Neurologia, Rua das Brañas 7-bajo-D, Mera, 15177 Oleiros, La Coruña, Galicia, Spain. pablo@quantuum.com

Brain Research. Molecular Brain Research
|March 3, 2004
PubMed

Insights

Alzheimer's disease brains show increased levels of amyloid precursor protein (APP) mRNA with protease inhibitor domains (KPI(+)). This specific increase in KPI(+) APP mRNA suggests a role in Alzheimer's pathology.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Alzheimer's disease (AD) is characterized by beta-amyloid deposits.
  • These deposits originate from the amyloid precursor protein (APP).
  • APP exists in various mRNA isoforms, with and without a Kunitz-type protease inhibitor (KPI) domain.

Purpose of the Study:

  • To investigate the differential expression of APP mRNA isoforms in Alzheimer's disease brains.
  • To test the hypothesis that aberrant catabolism of APP, potentially involving KPI isoforms, contributes to AD pathology.

Main Methods:

  • Quantification of APP mRNA isoforms using TaqMan real-time RT-PCR.
  • Analysis of 513 cerebral cortex samples from 90 AD and 81 control brains.
  • Statistical adjustment for age at death, brain pH, and gender.

Main Results:

  • A significant increase (28-50%) in KPI(+) APP mRNA levels was observed in AD brains compared to controls (p=0.002).
  • No significant change was found in KPI(-) APP mRNA (APP 695) levels (p=0.898).
  • The ratio of KPI(+) to KPI(-) mRNA isoforms was altered specifically in AD brains.

Conclusions:

  • The findings indicate a specific increase in KPI(+) APP mRNA in Alzheimer's disease brains.
  • This differential expression of APP isoforms may play a role in the pathogenesis of AD.
  • KPI(+) APP mRNA represents a potential biomarker or therapeutic target in Alzheimer's disease research.

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