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The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.

Isoform-Specific Effect of Apolipoprotein E on Cell Survival and β-Amyloid-Induced Toxicity in Rat Hippocampal Pyramidal Neuronal Cultures

Jordán, Joaquı́n, Galindo, Marı́a F., Miller, Richard J., Reardon, Catherine A., Getz, Godfrey S., LaDu, Mary Jo·1998·The Journal of Neuroscience
DOI 10.1523/jneurosci.18-01-00195.1998
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Abstract

Although the genetic link between the ε4 allele of apolipoprotein E (apoE) and Alzheimer’s disease is well established, the isoform-specific activity of apoE underlying this correlation remains unclear. To determine whether apoE influences the neurotoxic actions of β-amyloid (Aβ), we examined the effect of native preparations of apoE3 and E4 on Aβ-induced toxicity in primary cultures of rat hippocampal pyramidal neurons. The source of apoE was conditioned medium from HEK-293 cells stably transfected with human apoE3 or E4 cDNA. ApoE4 (10 μg/ml) alone was toxic to the cultures, whereas apoE3 had no effect. ApoE3 treatment prevented the toxicity induced by 10 μ m Aβ(1–40) or Aβ(25–35). The apoE3 protective effect appears to be specific to Aβ-induced toxicity, because apoE3 did not protect against the cytotoxicity produced by NMDA or staurosporine, nor did apoE3 affect the increase in intracellular calcium induced by either NMDA or KCl. ApoE3 had no effect on the toxicity produced by Aβ in the presence of receptor-associated protein, an inhibitor of apoE receptors, particularly the LDL-receptor-related protein. Interaction with apoE receptors may not mediate the toxic actions of apoE4, because receptor-associated protein did not affect apoE4-induced neurotoxicity. Consistent with our previous biochemical experiments, analysis of the culture medium revealed that SDS-stable apoE3:Aβ complex is present in greater abundance than apoE4:Aβ complex. Thus, the protection from Aβ-induced neurotoxicity afforded by apoE3 treatment may result from clearance of the peptide by apoE3:Aβ complex formation and uptake by apoE receptors.

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Crossref · 10.1523/jneurosci.18-01-00195.1998

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  • LRP-1 and its ligands α2-macroglobulin and apoE promote Aβ clearance in smooth muscle cells, neurons, and fibroblasts.

    “they promote A b clearance in smooth muscle cells (35), neurons (36, 38), and fibroblasts (37)”

    From Clearance of Alzheimer’s amyloid-β1-40 peptide from brain by LDL receptor–related protein-1 at the blood-brain barrier (2000) · cites this paper as [36]

    The citation is attached to the neuronal part of the sentence. In the Discussion (page unavailable), the paper proposes that apoE3 may protect cultured hippocampal neurons by clearing Aβ through neuronal LRP, and the RAP experiment supports that possibility. It does not establish Aβ clearance directly, and it does not show α2-macroglobulin promoting that clearance. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • ApoE and apoJ affect Aβ neurotoxicity.

    “In vitro, apoE and apoJ form stable complexes with A␤ (11, 16 -20), alter the aggregation of various A␤ peptides (21)(22)(23), and affect A␤ neurotoxicity (24 -27).”

    From Apolipoprotein E Receptors Mediate the Effects of β-Amyloid on Astrocyte Cultures (2000) · cites this paper as [25]

    The Discussion reports that apoE3 attenuated Aβ neurotoxicity in primary rat hippocampal neuron cultures, supporting the apoE part of the claim. Our copy does not report an effect of apoJ on Aβ neurotoxicity; apoJ appears in a reference about Aβ aggregation and oxidative stress, which does not establish the attributed neurotoxicity effect. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The addition of exogenous apoE protects against Aβ-induced toxicity in neuronal cell cultures and against Aβ-induced activation of astrocyte cultures.

    “The addition of exogenous apoE protects against A␤-induced toxicity in neuronal cell cultures, as well as A␤-induced activation of astrocyte cultures (24,25,38,52,53).”

    From Apolipoprotein E Receptors Mediate the Effects of β-Amyloid on Astrocyte Cultures (2000) · cites this paper as [25]

    The Results (‘ApoE4 is toxic to hippocampal pyramidal neurons’) and Discussion report that added apoE3, but not apoE4, protects rat hippocampal neuronal cultures from Aβ-induced toxicity. The paper uses astrocytes as a supporting feeder layer; it does not report whether apoE protects astrocyte cultures from Aβ-induced activation. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • ApoE, apoJ, and α2-macroglobulin have been shown to form a complex with Aβ that may facilitate clearance of the peptide.

    “ApoE, apoJ, and most recently ␣ 2 -macroglobulin have been shown to form a complex with A␤ that may facilitate clearance of the peptide (25-27, 50, 51).”

    From Apolipoprotein E Receptors Mediate the Effects of β-Amyloid on Astrocyte Cultures (2000) · cites this paper as [25]

    The paper reports an apoE3–Aβ complex in neuronal culture medium and, in the Discussion, proposes that binding may help clear Aβ. It does not establish the same clearance mechanism for apoJ or α2-macroglobulin; the apoJ complex appears only in a cited reference, and α2-macroglobulin is mentioned as a receptor name. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • A role for LRP-1 in promoting Aβ clearance in vitro in smooth muscle cells, neurons, and fibroblasts via α2M and apoE has been suggested, although at significantly slower rates than Aβ transport across the BBB.

    “A role for LRP-1 in promoting A b clearance in vitro in smooth muscle cells, neurons, and fibroblasts via a 2M and apoE has been suggested (35-38), although at significantly slower rates than the A b transport across the BBB demonstrated in this study.”

    From Clearance of Alzheimer’s amyloid-β1-40 peptide from brain by LDL receptor–related protein-1 at the blood-brain barrier (2000) · cites this paper as [36]

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Citations

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Metadata

Authors
Jordán, J., Galindo, M. F., Miller, R. J., Reardon, C. A., Getz, G. S., & LaDu, M. J.
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
1998-01-01
Volume
18
Issue
1
Pages
195-204
ISSN
  • 0270-6474
  • 1529-2401
DOI
10.1523/jneurosci.18-01-00195.1998
Cited by
139
References
5
Language
en
Licence
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 181 d)

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