Expression of human amyloid precursor protein in Drosophila melanogaster nerve cells causes a decrease in presynaptic

D I Rodin1, A L Schwarzman2, S V Sarantseva

  • 1Molecular and Radiation Biophysics Division, National Research Centre "Kurchatov Institute" B.P. Konstantinov Petersburg Nuclear Physics Institute, Gatchina, Russia rodin.dmitry@icloud.com.

Insights

Amyloid precursor protein (APP) and its fragments may regulate synaptic gene transcription. This study in fruit flies shows APP expression significantly reduces key presynaptic protein mRNA levels.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Alzheimer's disease is linked to amyloid precursor protein (APP).
  • APP cleavage produces amyloid-beta peptides, a major component of senile plaques.
  • The precise functions of APP and its fragments remain largely unknown.

Purpose of the Study:

  • To investigate the functional role of APP and its fragments.
  • To explore the potential impact of APP on synaptic gene expression.

Main Methods:

  • Exogenous expression of APP, APP-Swedish mutant, and truncated APP forms in Drosophila melanogaster.
  • Real-time polymerase chain reaction (RT-PCR) to quantify mRNA levels.

Main Results:

  • Exogenous expression of APP, APP-Swedish, or truncated forms significantly reduced mRNA levels of synaptotagmin-1.
  • A significant drop in neuronal synaptobrevin mRNA levels was observed.
  • Observed changes were statistically significant (P ≤ 0.05).

Conclusions:

  • APP or its fragments may play a role in regulating synaptic gene transcription.
  • Findings suggest a novel function for APP beyond its established role in Alzheimer's disease pathology.