Amyloid Precursor Protein and Alzheimer's Disease

Int J Mol Sci. 2023 Sep 30;24(19):14794. doi: 10.3390/ijms241914794.

Abstract

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders associated with age or inherited mutations. It is characterized by severe dementia in the late stages that affect memory, cognitive functions, and daily life overall. AD progression is linked to the accumulation of cytotoxic amyloid beta (Aβ) and hyperphosphorylated tau protein combined with other pathological features such as synaptic loss, defective energy metabolism, imbalances in protein, and metal homeostasis. Several treatment options for AD are under investigation, including antibody-based therapy and stem cell transplantation. Amyloid precursor protein (APP) is a membrane protein considered to play a main role in AD pathology. It is known that APP in physiological conditions follows a non-amyloidogenic pathway; however, it can proceed to an amyloidogenic scenario, which leads to the generation of extracellular deleterious Aβ plaques. Not all steps of APP biogenesis are clear so far, and these questions should be addressed in future studies. AD is a complex chronic disease with many factors that contribute to disease progression.

Keywords: Alzheimer’s disease; SRP-dependent targeting; amyloid beta; amyloid precursor protein (APP); membrane proteins; neurodegenerative disease; protein biogenesis; protein transport.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Humans
  • Membrane Proteins

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Membrane Proteins
  • APP protein, human