Cellular Trafficking of Amyloid Precursor Protein in Amyloidogenesis Physiological and Pathological Significance



The accumulation of excess intracellular or extracellular amyloid beta (Aβ) is one of the key pathological events in Alzheimer’s disease (AD). Aβ is generated from the cleavage of amyloid precursor protein (APP) by beta secretase-1 (BACE1) and gamma secretase (γ-secretase) within the cells. The endocytic trafficking of APP facilitates amyloidogenesis while at the cell surface, APP is predominantly processed in a non-amyloidogenic manner. Several adaptor proteins bind to both APP and BACE1, regulating their trafficking and recycling along the secretory and endocytic pathways. The phosphorylation of APP at Thr668 and BACE1 at Ser498, also influence their trafficking. Neurotrophins and proneurotrophins also influence APP trafficking through their receptors. In this review, we describe the molecular trafficking pathways of APP and BACE1 that lead to Aβ generation, the involvement of different signaling molecules or adaptor proteins regulating APP and BACE1 subcellular localization. We have also discussed how neurotrophins could modulate amyloidogenesis through their receptors.


APP BACE1 Cellular trafficking Gamma-secretase Amyloidogenesis 



This work was supported by NHMRC grants (XFZ&YJW) and University President’s Scholarship (NBM).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Noralyn Basco Mañucat-Tan
    • 1
  • Khalil Saadipour
    • 2
  • Yan-Jiang Wang
    • 3
  • Larisa Bobrovskaya
    • 1
  • Zhou Xin-Fu 
    • 1
  1. 1.School of Pharmacy and Medical Sciences, Sansom Institute for Health ResearchUniversity of South AustraliaAdelaideAustralia
  2. 2.Departments of Cell Biology, Physiology and Neuroscience, and Psychiatry, Skirball Institute of Biomolecular MedicineNew York University Langone School of MedicineNew YorkUSA
  3. 3.Department of Neurology and Center for Clinical Neuroscience, Daping HospitalThird Military Medical UniversityChongqingChina

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