Apolipoprotein E associates with beta amyloid peptide of Alzheimer's disease to form novel monofibrils. Isoform apoE4 associates more efficiently than apoE3.

Sanan, David A.; Weisgraber, Karl H.; Russell, Stephen J.; Mahley, Robert W.; Huang, David; Saunders, Ann M.; Schmechel, Donald E.; Wısnıewskı, Thomas; Frangione, Blas; Roses, Allen D.

doi:10.1172/jci117407

Cited by 385 publications

(245 citation statements)

References 25 publications

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“…The formation in this model system of ,B-peptide deposits with the tinctural characteristics of classic amyloid allows investigation of factors postulated to modulate /3-peptide aggregation, many of which have only been examined in vitro. (43,44); these studies can be readily replicated in this model system. In addition, mutated ,3-peptide variants can be expressed in this system to identify residues critical for formation of thioflavin S-reactive deposits.…”

Section: Discussionmentioning

confidence: 73%

Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans.

Link

1995

Proc. Natl. Acad. Sci. U.S.A.

621

511

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Transgenic Caenorhabditis elegans nematodes have been engineered to express potentially amyloidic human proteins. These animals contain constructs in which the muscle-specific unc-54 promoter/enhancer of C. elegans drives the expression of the appropriate coding regions derived from human cDNA clones. Animals containing constructs expressing the 42-amino acid f3-amyloid peptide (derived from human amyloid precursor protein cDNA) produce muscle-specific deposits immunoreactive with anti-,3-amyloid polyclonal and monoclonal antibodies. A subset of these deposits also bind the amyloid-specific dye thioflavin S, indicating that these deposits have the tinctural characteristics of classic amyloid. Coexpression of f3-peptide and transthyretin, a protein implicated in preventing the formation of insoluble 13-amyloid, leads to a dramatic reduction in the number of dye-reactive deposits. These results suggest that this invertebrate model may be useful for in vivo investigation of factors that modulate amyloid formation.

show abstract

Section: Discussionmentioning

confidence: 73%

Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans.

Link

1995

Proc. Natl. Acad. Sci. U.S.A.

621

511

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“…Our results suggest that the choroid plexus is the major source of apoE in CSF. Because the choroid plexus clears brain A␤ peptides by transporting them from CSF to blood (Crossgrove et al, 2005) and because apoE isoforms interact differently with A␤ peptides (Strittmatter et al, 1993b;LaDu et al, 1994LaDu et al, , 1995Ma et al, 1994;Sanan et al, 1994;Wisniewski et al, 1994), apoE generated by the choroid plexus might affect A␤ clearance in an isoform-specific manner. In fact, apoE knock-out mice have higher A␤ levels in CSF than wild-type mice (DeMattos et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Profile and Regulation of Apolipoprotein E (ApoE) Expression in the CNS in Mice with Targeting of Green Fluorescent Protein Gene to the ApoE Locus

Xu¹,

Bernardo²,

Walker³

et al. 2006

J. Neurosci.

420

333

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To study the profile and regulation of apolipoprotein E (apoE) expression in the CNS, we generated mice in which apoE expression can be detected in vivo with unprecedented sensitivity and resolution. cDNA encoding enhanced green fluorescent protein (EGFP) with a stop codon was inserted by gene targeting into the apoE gene locus (EGFP apoE ) immediately after the translation initiation site. Insertion of EGFP into one apoE allele provides a real-time location marker of apoE expression in vivo; the remaining allele is sufficient to maintain normal cellular physiology. In heterozygous EGFP apoE mice, EGFP was highly expressed in hepatocytes and peritoneal macrophages. EGFP was also expressed in brain astrocytes; however some astrocytes (ϳ25%) expressed no EGFP, suggesting that a subset of these cells does not express apoE. EGFP was expressed in Ͻ10% of microglia after kainic acid treatment, suggesting that microglia are not a major source of brain apoE. Although hippocampal neurons did not express EGFP under normal conditions, kainic acid treatment induced intense expression of EGFP in injured neurons, demonstrating apoE expression in neurons in response to excitotoxic injury. The neuronal expression was confirmed by in situ hybridization of mouse apoE mRNA and by anti-apoE immunostaining. Smooth muscle cells of large blood vessels and cells surrounding small vessels in the CNS also strongly expressed EGFP, as did cells in the choroid plexus. EGFP apoE reporter mice will be useful for studying the regulation of apoE expression in the CNS and might provide insights into the diverse mechanisms of apoE4-related neurodegeneration.

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“…In vitro and in vivo studies suggest that apoE may influence Ab seeding and fibrillogenesis, as well as soluble Ab clearance. Lipid-free and lipidated ( physiological) forms of apoE can interact with Ab in vitro (Strittmatter et al 1993b;LaDu et al 1994;Sanan et al 1994;Aleshkov et al 1997;Yang et al 1997;Tokuda et al 2000). Most studies show that the efficiency of complex formation between lipidated apoE and Ab follows the order of apoE2 .…”

Section: Genetic Clinical and Biomarker Observations On Relationshimentioning

confidence: 99%

Apolipoprotein E and Apolipoprotein E Receptors: Normal Biology and Roles in Alzheimer Disease

Holtzman

Herz²,

2012

Cold Spring Harbor Perspectives in Medicine

681

602

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Apolipoprotein E associates with beta amyloid peptide of Alzheimer's disease to form novel monofibrils. Isoform apoE4 associates more efficiently than apoE3.

Cited by 385 publications

References 25 publications

Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans.

Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans.

Profile and Regulation of Apolipoprotein E (ApoE) Expression in the CNS in Mice with Targeting of Green Fluorescent Protein Gene to the ApoE Locus

Apolipoprotein E and Apolipoprotein E Receptors: Normal Biology and Roles in Alzheimer Disease

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