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

Courtney Lane-Donovan, Joachim Herz

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 e(open)4 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. Reelin signaling through apolipoprotein E (ApoE) receptors activates a signaling cascade that protects against amyloid-beta (Aβ) at the level of N-methyl-d-aspartate receptor (NMDAR) endocytosis, actin polymerization, and tau phosphorylation.ApoE4 induces neuronal resistance to Reelin by impairing the recycling of vesicles containing ApoE receptors, which results in reduced surface expression of the receptors.ApoE receptors on the presynaptic neuron affect spontaneous vesicle release by increasing the mobilization of vesicle-associated membrane protein 7 (VAMP7)-containing vesicles.Astrocytes express ApoE receptors, which may play a role in gliotransmission and synaptic pruning.

Original languageEnglish (US)
JournalTrends in Endocrinology and Metabolism
DOIs
StateAccepted/In press - 2016

Fingerprint

Low Density Lipoprotein Receptor-Related Protein-1
Apolipoprotein E4
Apolipoproteins E
Synapses
Alzheimer Disease
Astrocytes
R-SNARE Proteins
Dendritic Spines
Neuronal Plasticity
Family Health
Presynaptic Terminals
Recycling
Endocytosis
Amyloid
Polymerization
Neurodegenerative Diseases
Population
Signs and Symptoms
Actins
Protein Isoforms

Keywords

  • Calcium homeostasis
  • Dendrite
  • Endosome
  • LRP
  • NMDA receptor
  • Reelin
  • Synaptic dysfunction

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease. / Lane-Donovan, Courtney; Herz, Joachim.

In: Trends in Endocrinology and Metabolism, 2016.

Research output: Contribution to journalArticle

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