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

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

Author information

1
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Center for Translational Neurodegeneration Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: Courtney.Lane@utsouthwestern.edu.
2
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Center for Translational Neurodegeneration Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Center for Neuroscience, Department of Neuroanatomy, Albert Ludwig University, Freiburg, Germany. Electronic address: Joachim.Herz@utsouthwestern.edu.

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

PMID:
28057414
PMCID:
PMC5366078
DOI:
10.1016/j.tem.2016.12.001
[Indexed for MEDLINE]
Free PMC Article

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