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Molecular pathogenesis of apolipoprotein E-mediated amyloidosis in late-onset Alzheimer's disease.
Cell Mol Life Sci 1999; 56(3-4):268-79CM

Abstract

Apolipoprotein E (apoE) epsilon4 allele is a genetic risk factor for late-onset familial and sporadic Alzheimer's disease (AD). In the central nervous system, apoE is secreted mainly by astrocytes as a constituent of high-density lipoproteins. A recent study using apoE knockout mice provided strong evidence that apoE promotes cerebral deposition of amyloid beta protein (Abeta). However, no clear explanation of the pathogenesis of apoE-induced AD has been provided. Here we discuss two possible mechanisms by which apoE might enhance Abeta deposition. One is the intracellular pathway in which apoE is internalized by neurons and induces lysosomal accumulation of Abeta and amyloidogenic APP (amyloid precursor protein) fragments, leading to neuronal death. The other is the extracellular pathway in which apoE-containing lipoproteins are trapped by Abeta1-42 deposits mobilizing soluble Abeta peptides and consequently enlarge amyloid plaques. These two mechanisms may operate at different stages of AD pathogenesis and suggest a chaperone-like function for the apoE molecule

Authors+Show Affiliations

Department of Neuroscience, Osaka City University Medical School, Osaka, Japan.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

11212354

Citation

Tomiyama, T, et al. "Molecular Pathogenesis of Apolipoprotein E-mediated Amyloidosis in Late-onset Alzheimer's Disease." Cellular and Molecular Life Sciences : CMLS, vol. 56, no. 3-4, 1999, pp. 268-79.
Tomiyama T, Corder EH, Mori H. Molecular pathogenesis of apolipoprotein E-mediated amyloidosis in late-onset Alzheimer's disease. Cell Mol Life Sci. 1999;56(3-4):268-79.
Tomiyama, T., Corder, E. H., & Mori, H. (1999). Molecular pathogenesis of apolipoprotein E-mediated amyloidosis in late-onset Alzheimer's disease. Cellular and Molecular Life Sciences : CMLS, 56(3-4), pp. 268-79.
Tomiyama T, Corder EH, Mori H. Molecular Pathogenesis of Apolipoprotein E-mediated Amyloidosis in Late-onset Alzheimer's Disease. Cell Mol Life Sci. 1999 Oct 15;56(3-4):268-79. PubMed PMID: 11212354.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular pathogenesis of apolipoprotein E-mediated amyloidosis in late-onset Alzheimer's disease. AU - Tomiyama,T, AU - Corder,E H, AU - Mori,H, PY - 2001/2/24/pubmed PY - 2001/3/7/medline PY - 2001/2/24/entrez SP - 268 EP - 79 JF - Cellular and molecular life sciences : CMLS JO - Cell. Mol. Life Sci. VL - 56 IS - 3-4 N2 - Apolipoprotein E (apoE) epsilon4 allele is a genetic risk factor for late-onset familial and sporadic Alzheimer's disease (AD). In the central nervous system, apoE is secreted mainly by astrocytes as a constituent of high-density lipoproteins. A recent study using apoE knockout mice provided strong evidence that apoE promotes cerebral deposition of amyloid beta protein (Abeta). However, no clear explanation of the pathogenesis of apoE-induced AD has been provided. Here we discuss two possible mechanisms by which apoE might enhance Abeta deposition. One is the intracellular pathway in which apoE is internalized by neurons and induces lysosomal accumulation of Abeta and amyloidogenic APP (amyloid precursor protein) fragments, leading to neuronal death. The other is the extracellular pathway in which apoE-containing lipoproteins are trapped by Abeta1-42 deposits mobilizing soluble Abeta peptides and consequently enlarge amyloid plaques. These two mechanisms may operate at different stages of AD pathogenesis and suggest a chaperone-like function for the apoE molecule SN - 1420-682X UR - https://www.unboundmedicine.com/medline/citation/11212354/Molecular_pathogenesis_of_apolipoprotein_E_mediated_amyloidosis_in_late_onset_Alzheimer's_disease_ L2 - https://dx.doi.org/10.1007/s000180050428 DB - PRIME DP - Unbound Medicine ER -