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Sortilin, a novel APOE receptor implicated in Alzheimer disease

Item Type:Editorial
Title:Sortilin, a novel APOE receptor implicated in Alzheimer disease
Creators Name:Carlo, A.S.
Abstract:In the brain, apolipoprotein E (APOE) delivers cholesterol-rich lipoproteins to neurons to support synaptogenesis and maintenance of synaptic connections. Three APOE alleles exist in the human population with {epsilon}4 being an Alzheimer disease (AD) risk gene and {epsilon}2 being protective relative to the common {epsilon}3 variant. Many hypotheses have been advanced concerning allele-specific effects of APOE on neurodegeneration including effects on A{beta} clearance, synaptic transmission, or neurotoxicity. Central to most proposed APOE functions is its interaction with receptors that mediate cellular uptake of this ligand. Several members of the LDL receptor gene family have been implicated as APOE receptors in the (patho)physiology of APOE in the brain, yet their specific modes of action in AD remain controversial. Recently, the pro-neurotrophin receptor sortilin has been identified as a novel APOE receptor in neurons. Ablation of sortilin expression in mice results in accumulation of APOE and A{beta} in the brain. Also, primary neurons lacking sortilin exhibit significantly impaired uptake of APOE/A{beta} complexes. Despite increased brain APOE levels, sortilin-deficient animals recapitulate anomalies in brain lipid homeostasis seen in APOE null mice, indicating functional deficiency in APOE uptake pathways. Taken together, these findings suggest a link between A{beta} catabolism and pro-neurotrophin signaling converging on this receptor pathway.
Keywords:Alzheimer's Disease, LDLR Gene Family, Amyloid {beta}, Apolipoprotein E, Neurotrophins, Sortilin, Animals
Publisher:Landes Bioscience
Page Range:378-382
Date:September 2013
Official Publication:https://doi.org/10.1523/JNEUROSCI.2425-12.2013
PubMed:View item in PubMed

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