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Astrocyte lipoproteins, effects of apoE on neuronal function, and role of apoE in amyloid-beta deposition in vivo.
Microsc Res Tech 2000; 50(4):297-304MR

Abstract

The genetic association between the E4 isoform of apolipoprotein E (apoE) and increased risk for Alzheimer's disease (AD) has prompted interest in the neurobiology of apoE and the possible relationship between lipoprotein metabolism in the brain and neurodegenerative disease. ApoE, a product of astrocytes, is abundant in brain and in cerebrospinal fluid (CSF) where it is found in lipoproteins the size of large plasma high-density lipoproteins (HDL). Cultured astrocytes also secrete apoE/HDL, although the lipid and apoprotein composition of these nascent particles differs from that found in CSF, suggesting possible functional differences. In vitro studies have demonstrated isoform-specific effects of apoE on neurite outgrowth, neuronal plasticity, neurotoxicity, lipid peroxidation, oxidative injury, binding to cytoskeletal proteins, and interactions with amyloid-beta (Abeta), a primary component of senile plaques in AD. A number of these proposed functions have also been assessed in apoE -/- mice and transgenic mice expressing human apoE3 or apoE4. Importantly, analysis of transgenic mice overexpressing a mutant form of the human amyloid precursor protein (APP(V717F)) in the presence of mouse apoE, no apoE, or human apoE3 or E4 has demonstrated a critical and isoform-specific role for apoE in neuritic plaque formation, a pathologic hallmark of AD. Together, these data have provided important clues as to possible mechanism(s) by which apoE genotype modifies AD risk.

Authors+Show Affiliations

Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, Missouri 63110, USA. fagana@neuro.wustl.eduNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

10936884

Citation

Fagan, A M., and D M. Holtzman. "Astrocyte Lipoproteins, Effects of apoE On Neuronal Function, and Role of apoE in Amyloid-beta Deposition in Vivo." Microscopy Research and Technique, vol. 50, no. 4, 2000, pp. 297-304.
Fagan AM, Holtzman DM. Astrocyte lipoproteins, effects of apoE on neuronal function, and role of apoE in amyloid-beta deposition in vivo. Microsc Res Tech. 2000;50(4):297-304.
Fagan, A. M., & Holtzman, D. M. (2000). Astrocyte lipoproteins, effects of apoE on neuronal function, and role of apoE in amyloid-beta deposition in vivo. Microscopy Research and Technique, 50(4), pp. 297-304.
Fagan AM, Holtzman DM. Astrocyte Lipoproteins, Effects of apoE On Neuronal Function, and Role of apoE in Amyloid-beta Deposition in Vivo. Microsc Res Tech. 2000 Aug 15;50(4):297-304. PubMed PMID: 10936884.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Astrocyte lipoproteins, effects of apoE on neuronal function, and role of apoE in amyloid-beta deposition in vivo. AU - Fagan,A M, AU - Holtzman,D M, PY - 2000/8/11/pubmed PY - 2000/10/7/medline PY - 2000/8/11/entrez SP - 297 EP - 304 JF - Microscopy research and technique JO - Microsc. Res. Tech. VL - 50 IS - 4 N2 - The genetic association between the E4 isoform of apolipoprotein E (apoE) and increased risk for Alzheimer's disease (AD) has prompted interest in the neurobiology of apoE and the possible relationship between lipoprotein metabolism in the brain and neurodegenerative disease. ApoE, a product of astrocytes, is abundant in brain and in cerebrospinal fluid (CSF) where it is found in lipoproteins the size of large plasma high-density lipoproteins (HDL). Cultured astrocytes also secrete apoE/HDL, although the lipid and apoprotein composition of these nascent particles differs from that found in CSF, suggesting possible functional differences. In vitro studies have demonstrated isoform-specific effects of apoE on neurite outgrowth, neuronal plasticity, neurotoxicity, lipid peroxidation, oxidative injury, binding to cytoskeletal proteins, and interactions with amyloid-beta (Abeta), a primary component of senile plaques in AD. A number of these proposed functions have also been assessed in apoE -/- mice and transgenic mice expressing human apoE3 or apoE4. Importantly, analysis of transgenic mice overexpressing a mutant form of the human amyloid precursor protein (APP(V717F)) in the presence of mouse apoE, no apoE, or human apoE3 or E4 has demonstrated a critical and isoform-specific role for apoE in neuritic plaque formation, a pathologic hallmark of AD. Together, these data have provided important clues as to possible mechanism(s) by which apoE genotype modifies AD risk. SN - 1059-910X UR - https://www.unboundmedicine.com/medline/citation/10936884/Astrocyte_lipoproteins_effects_of_apoE_on_neuronal_function_and_role_of_apoE_in_amyloid_beta_deposition_in_vivo_ L2 - https://doi.org/10.1002/1097-0029(20000815)50:4<297::AID-JEMT9>3.0.CO;2-C DB - PRIME DP - Unbound Medicine ER -