ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease

Trends Endocrinol Metab. 2017 Apr;28(4):273-284. doi: 10.1016/j.tem.2016.12.001. Epub 2017 Jan 2.

Abstract

As the population ages, neurodegenerative diseases such as Alzheimer's disease (AD) are becoming a significant burden on patients, their families, and health-care systems. Neurodegenerative processes may start up to 15 years before outward signs and symptoms of AD, as evidenced by data from AD patients and mouse models. A major genetic risk factor for late-onset AD is the ɛ4 isoform of apolipoprotein E (ApoE4), which is present in almost 20% of the population. In this review we discuss the contribution of ApoE receptor signaling to the function of each component of the tripartite synapse - the axon terminal, the postsynaptic dendritic spine, and the astrocyte - and examine how these systems fail in the context of ApoE4 and AD.

Keywords: LRP; NMDA receptor; Reelin.; calcium homeostasis; dendrite; endosome; synaptic dysfunction.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Animals
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism*
  • Disease Models, Animal
  • Female
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-1 / genetics
  • Low Density Lipoprotein Receptor-Related Protein-1 / metabolism*
  • Male
  • Reelin Protein
  • Synapses / genetics
  • Synapses / metabolism*

Substances

  • Apolipoproteins E
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Reelin Protein
  • RELN protein, human
  • Reln protein, mouse