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Related Experiment Video

Updated: Jan 29, 2026

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APP depletion alters selective pre- and post-synaptic proteins.

Isak Martinsson1, Estibaliz Capetillo-Zarate2, Mathilde Faideau1

  • 1Experimental Dementia Research Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.

Molecular and Cellular Neurosciences
|February 15, 2019
PubMed
Summary

The amyloid precursor protein (APP) is crucial for normal synapse composition. Its absence in neurons leads to increased levels of certain synaptic proteins, contrasting with findings in Alzheimer's disease models.

Keywords:
AMPA receptorsAlzheimer's diseaseAmyloidAmyloid precursor proteinSynapse

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • The precise function of the Alzheimer's disease-linked amyloid precursor protein (APP) in the brain is not fully understood.
  • Previous research indicates APP is vital for synaptic development and function, with its absence potentially harming neuronal structures.
  • The role of APP in mature synapses is complex due to its developmental functions.

Purpose of the Study:

  • To investigate the impact of amyloid precursor protein (APP) knockout on the composition of mature synapses.
  • To compare synaptic protein and receptor levels in APP knockout neurons versus wild-type neurons.
  • To explore the effects of APP deficiency in both cultured neurons and in vivo mouse models.

Main Methods:

  • Analysis of synaptic protein and receptor levels in primary mouse neurons lacking APP (knockout) compared to wild-type controls.
  • Investigation using both in vitro cell cultures and in vivo studies in young and adult mice.
  • Utilized RNA interference (RNAi) knockdown as an additional method to study APP's role.

Main Results:

  • Significant alterations in selective pre- and post-synaptic proteins and receptors were observed in APP knockout neurons.
  • Conversely to findings in Alzheimer's disease models, APP knockout led to selective increases in synaptic proteins like GluA1.
  • These changes were consistent across cultured neurons and in the brains of APP knockout mice.

Conclusions:

  • Amyloid precursor protein (APP) plays a critical role in maintaining the normal composition of synapses.
  • The absence of APP has distinct effects on synaptic proteins, differing from the changes seen in Alzheimer's disease-related APP mutations.
  • These findings highlight APP's importance in regulating synaptic structure and function throughout life.