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Changes in apolipoprotein E expression in response to dietary and pharmacological modulation of cholesterol

  • Alzheimer’s Therapeutics: Lipid Lowering
  • Published:
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Abstract

Apolipoprotein E (ApoE) influences the risk of late onset Alzheimer’s disease (AD) in an isoform-dependent manner, such that the presence of the apoE ε4 allele increases the risk of AD while the presence of the apoE ε2 allele appears to be protective. Although a number of ApoE functions are isoform dependent and may underlie the “risk factor” activity of AD, its ability to bind amyloid β peptides and influence their clearance and/or deposition has gained strong experimental support. Evidence suggests that in addition to genotype, increased ApoE transcription can contribute to AD risk. There is growing evidence in support of the hypothesis that disrupted cholesterol metabolism is an early risk factor for AD. Studies in animal models have shown that chronic changes in cholesterol metabolism associate with changes in brain Aβ accumulation, a process instrumental for establishing AD pathology. ApoE mediates cholesterol homeostasis in the body and is a major lipid carrier in brain. As such, its expression in the periphery and in brain changes in response to changes in cholesterol metabolism. Here, we used a transgenic mouse model of Alzheimer’s amyloidosis to examine whether the diet-induced or pharmacologically induced changes in plasma cholesterol that result in altered brain amyloidosis also affect ApoE content in liver and in brain. We found that chronic changes in total cholesterol in plasma lead to changes in ApoE mRNA levels in brain. We also found that cholesterol loading of primary glial cells increases cellular and secreted ApoE levels and that long-term treatment of astrocytes and microglia with statins leads to a decrease in the cellular and/or secreted ApoE. These observations suggest that disrupted cholesterol metabolism may increase the risk of developing AD in part due to the effect of cholesterol on brain ApoE expression.

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References

  • Artiga M. J., Bullido M. J., Frank A., Sastre I., Recuero M., Garcia M. A., et al. (1998) Risk for Alzheimer’s disease correlates with transcriptional activity of the APOE gene. Hum. Mol. Genet. 12, 1887–1892.

    Article  Google Scholar 

  • Bales K. R., Verina T., Cummins D. J., Du Y., Dodel R. C., Saura J., et al. (1999) Apolipoprotein E is essential for amyloid deposition in the APPV717F transgenic mouse model of Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 96, 15,233–15,238.

    Article  CAS  Google Scholar 

  • Bjorkhem I., Meaney S., and Diczfalusy U. (2002) Oxysterols in human circulation: which role do they have? Curr. Opin. Lipidol. 13, 247–253.

    Article  PubMed  CAS  Google Scholar 

  • Bullido M. J. and Valdivieso F. (2000) Apolipoprotein E gene polymorphisms in Alzheimer’s disease. Microsc. Res. Tech. 50, 261–267.

    Article  PubMed  CAS  Google Scholar 

  • Buxbaum J. D., Cullen E. I., and Friedhoff L. T. (2002) Pharmacological concentrations of the HMGCoA reductase inhibitor lovastatin decrease the formation of the Alzheimer β-amyloid peptide in vitro and in patients. Front Biosci. 7, 50–59.

    Article  Google Scholar 

  • Canoll P. D., Petanceska S., Schlessinger J., and Musacchio J. M. (1996) Three forms of RPTP-beta are differentially expressed during gliogenesis in the developing rat brain and during glial cell differentiation in culture. J. Neurosci. Res. 44, 199–215.

    Article  Google Scholar 

  • Cole G. and Ard M. D. (2000) Influence of lipoproteins on microglial degradation of Alzheimer’s amyloid beta-protein. Microsc. Res. Tech. 15, 316–324.

    Article  Google Scholar 

  • Corder E. H., Saunders A. M., Strittmatter W. J., et al. (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261, 921–923.

    Article  PubMed  CAS  Google Scholar 

  • Corder E. H., Saunders A. M., Risch N. J., et al. (1994) Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nat. Genet. 2, 180–184.

    Article  Google Scholar 

  • Driscoll D. M., Mazzone T., Matsushima T., and Getz G. S. (1990) Apoprotein E biosynthesis in the cholesterol-fed guinea pig. Arteriosclerosis 10, 31–39.

    PubMed  CAS  Google Scholar 

  • Eckert G. P., Kirsch C., and Mueller, W. E. (2001) Differential effects of lovastatin treatment on brain cholesterol levels in normal and Apo-E deficient mice. Neuropharmacol. Neurotoxicol. 12, 883–887.

    CAS  Google Scholar 

  • Ehehalt R., Keller P., Haass C., Thiele C., and Simons K. (2003) Amyloidogenic processing of the Alzheimer beta-amyloid precursor protein depends on lipid rafts. J. Cell Biol. 160, 113–123.

    Article  PubMed  CAS  Google Scholar 

  • Fagan A. and Holtzman D. M. (2000) Astrocyte Lipoproteins, Effects of ApoE on neuronal function, and role of ApoE in amyloid β deposition in vivo. Microsc. Res. Tech. 50, 297–304.

    Article  PubMed  CAS  Google Scholar 

  • Fagan A. M., Holtzman D. M., Munson G., Mathur T., Schneider D., Chang L. K., et al. (1999) Unique lipoproteins secreted by primary astrocytes from wild type, ApoE (-/-), and human ApoE transgenic mice. J. Biol. Chem. 274, 30,001–30,007.

    CAS  Google Scholar 

  • Fagan A. M., Watson M., Parsadanian M., Bales K. R., Paul S. M., and Holtzman D. M. (2002) Human and murine ApoE markedly alters Abeta metabolism before and after plaque formation in a mouse model of Alzheimer’s disease. Neurobiol. Dis. 9, 305–318.

    Article  PubMed  CAS  Google Scholar 

  • Fassbender K., Simons M., Bergmann C., Stroick M., Lutjohann D., Keller P., et al. (2001) Simvastatin strongly reduces levels of Alzheimer’s disease beta-amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo. Proc. Natl. Acad. Sci. U.S.A. 98, 5856–5861.

    Article  PubMed  CAS  Google Scholar 

  • Gandy S. and Petanceska S. (2000) Regulation of Alzheimer beta-amyloid precursor trafficking and metabolism. Biochim. Biophys. Acta 502, 44–52.

    Google Scholar 

  • Gueguen Y., Bertrand P., Ferrari L., Batt A. M., and Siest G. (2001) Control of apolipoprotein E secretion by 25-hydroxycholesterol and proinflammatory cytokines in the human astrocytoma cell line CCF-STTG1. Cell Biol. Toxicol. 17, 191–199.

    Article  PubMed  CAS  Google Scholar 

  • Guo L., LaDu M. J., and Van Eldik L. J. (2002) ApoE down regulates pro-inflammatory responses induced by oligomeric Aβ in activated glia. Soc. Neurosci. Abstr. 883, 12.

    Google Scholar 

  • Hagberg J. M., Kenneth R. W., and Ferrell R. E. (2000) APOE gene and gene-environment effects on plasma lipoprotein-lipid levels. Physiol. Genomics 4, 101–108.

    PubMed  CAS  Google Scholar 

  • Hamelin B. A. and Turgeon T. (1998) Hydrophilicity/lipophilicity: relevance for the pharmacology and clinical effects of HMG-CoA reductase inhibitors. Trends Pharmacol. Sci. 19, 26–37.

    Article  PubMed  CAS  Google Scholar 

  • Hartmann T. (2001) Cholesterol, A beta and Alzheimer’s disease. Trends Neurosci. 11(Suppl.), S45-S48.

    Article  Google Scholar 

  • Holcomb L., Gordon M. N., McGowan E., Yu X., Benkovic S., Jantzen P., et al. (1998) Accelerated Alzheimer’s type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin transgenes. Nat. Med. 4, 97–100.

    Article  PubMed  CAS  Google Scholar 

  • Holtzman D. M. (2001) Role of apoe/Abeta interactions in the pathogenesis of Alzheimer’s disease and cerebral amyloid angiopathy. J. Mol. Neurosci. 17, 147–155.

    Article  PubMed  CAS  Google Scholar 

  • Holtzman D. M., Bales K. R., Wu S., Bhat P., Parsadanian M., Fagan A. M., et al. (1999) Expression of human apolipoprotein E reduces amyloid-beta deposition in a mouse model of Alzheimer’s disease. J. Clin. Invest. 103, R15-R21.

    Article  PubMed  CAS  Google Scholar 

  • Holtzman D. M., Fagan A. M., Mackey B., Tenkova T., Sartorius L., Paul S. M., et al. (2000a) Apolipoprotein E facilitates neuritic and cerebrovascular plaque formation in an Alzheimer’s disease model. Ann. Neurol. 47, 739–747.

    Article  PubMed  CAS  Google Scholar 

  • Holtzman D. M., Bales K. R., Tenkova T., Fagan A. M., Parsadanian M., Sartorius L. J., et al. (2000b) Apolipoprotein-isoform dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 97, 2892–2897.

    Article  PubMed  CAS  Google Scholar 

  • Honda A., Salen G., Nguyen L. B., Xu G., Tint G. S., Batta A. K., and Shefer S. (1998) Regulation of early cholesterol biosynthesis in rat liver: effects of sterols, bile acids, lovastatin, and BM 15.766 on 3-hydroxy-3-methylglutaryl coenzyme A synthase and acetoacetyl coenzyme A thiolase activities. Hepatology 27, 154–159.

    Article  PubMed  CAS  Google Scholar 

  • Howland D. S., Trusko S. P., Savage M. J., et al. (1998) Modulation of secreted beta-amyloid precursor protein and amyloid beta-peptide in brain by cholesterol. J. Biol. Chem. 273, 16,576–16,582.

    Article  CAS  Google Scholar 

  • Jarvik G. P., Austin M. A., Fabsitz R. R., Auwerx J., Reed T., Christian J. C., and Deeb S. (1994) Genetic influences on age related change in total cholesterol, low density lipoprotein cholesterol, triglyceride levels longitudinal apolipoprotein E genotype effects. Genet. Epidemiol. 11, 375–384.

    Article  PubMed  CAS  Google Scholar 

  • Jarvik G. P., Wijsman E. M., Kukull W. A., Schellenberg G. D., Yu C., and Larson E. B. (1995) Interactions of apolipoprotein E genotype, total cholesterol level, age, and sex in prediction of Alzheimer’s disease: a case-control study. Neurology 45, 1092–1096.

    PubMed  CAS  Google Scholar 

  • Jick H., Zornberg G. L., Jick S. S., Seshadri S., and Drachman D. A. (2000) Statins and the risk of dementia. Lancet 356, 1627–1631.

    Article  PubMed  CAS  Google Scholar 

  • Jessen F., Rao M. L., von Bergmann K., and Heun R. (2000) Plasma 24S-hydroxycholesterol (cerebrosterol) is increased in Alzheimer and vascular demented patients. J. Lipid. Res. 41, 195–198.

    PubMed  Google Scholar 

  • Kivipelto M., Helkala E. L., Hanninen T., Laakso M. P., Hallikainen M., Alhainen K., et al. (2001) Midlife vascular risk factors and late life cognitive impairment: A population-based study. Neurology 56, 1683–1689.

    PubMed  CAS  Google Scholar 

  • Kivipelto M., Helkala E. L., Laakso M. P., Hanninen T., Hallikainen M., Alhainen K., et al. (2002) Apolipoprotein E e4 allele, ellevated midlife total cholesterol level and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer’s disease. Ann. Intern. Med. 137, 149–155.

    PubMed  CAS  Google Scholar 

  • Kojro E., Gimpi G., Lammich S., Marz W., and Fahrenzolc (2001) Low cholesterol stimulates the non-amyloidogenic pathway by its effect on the a-secretase ADAM 10. Proc. Natl. Acad. Sci. U.S.A. 98, 5815–5820.

    Article  PubMed  CAS  Google Scholar 

  • Kolsch H., Lutjohann D., Ludwig M., Schulte A., Ptok U., Jessen F., et al. (2002) Polymorphism in the cholesterol 24S-hydroxylase gene is associated with Alzheimer’s disease. Mol. Psychiatry 7, 899–902.

    Article  PubMed  CAS  Google Scholar 

  • Koudinov A. R., Berezov T. T., and Koudinova N. V. (2002) Cholesterol and Alzheimer’s disease: is there a link? Neurology 58, 1135.

    PubMed  Google Scholar 

  • LaDu M. J., Shah J. A., Reardon C. A., Getz G. S., Bu G., Hu J., et al. (2001) Apolipoprotein E and apolipoprotein E receptors modlulate A beta-induced glial neuroinflammatory responses. Neurochem. Int. 39, 427–434.

    Article  PubMed  CAS  Google Scholar 

  • Laffitte B. A., Repa J. J., Joseph S. B., Wilpitz D. C., Kast H. R., Mangelsdorf D. J., and Tontonoz P. (2001) LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes. Proc. Natl. Acad. Sci. U.S.A. 98, 507–512.

    Article  PubMed  CAS  Google Scholar 

  • Lambert J. C., Mann D., Goumidi L., Harris J., Amouyel P., Iwatsubo T., et al. (2001) Effect of the APOE promoter polymorphisms on cerebral amyloid peptide deposition in Alzheimer’s disease. Lancet 357, 608–609.

    Article  PubMed  CAS  Google Scholar 

  • Laskowitz D. T., Horsburgh K., and Roses A. D. (1998) Apolipoprotein E and the CNS response to injury. J. Cereb. Blood Flow Metab. 18, 465–471.

    Article  PubMed  CAS  Google Scholar 

  • Laws S. M., Clarnette R. M., Taddei K., Martins G., Paton A., Hallmayer J., et al. (2002) APOE-epsilon4 and APOE-491A polymorphisms in individuals with subjective memory loss. Mol. Psychiatry 7, 768–775.

    Article  PubMed  CAS  Google Scholar 

  • Levin-Allerhand J. A., Lominska C. E., and Smith J. D. (2002) Increased amyloid-levels in APPSWE transgenic mice treated chronically with a physiological high-fat high-cholesterol diet. J. Nutr. Health Aging 6, 315–319.

    PubMed  CAS  Google Scholar 

  • Lynch J. R., Morgan D., Mance J., Mathew W. D., and Laskowitz D. T. (2001) Apolipoprotein E modulates glial activation and the endogenous central nervous system inflammatory response. J. Neuroimmunol. 114, 107–113.

    Article  PubMed  CAS  Google Scholar 

  • Mazzone T., Basheeruddin K., and Poulos C. (1989) Regulation of macrophage apolipoprotein E gene expression by cholesterol. J. Lipid Res. 30, 1055–1064.

    PubMed  CAS  Google Scholar 

  • Mazzone T., Gump H., Diller P., and Getz G. S. (1987) Macrophage free cholesterol content regulates apolipoprotein E synthesis. J. Biol. Chem. 262, 11,657–11,662.

    CAS  Google Scholar 

  • Mauch D. H., Nagler K., Schumacher S., Goritz C., Muller E. C., Otto A., and Pfrieger F. W. (2001) CNS synaptogenesis promoted by glia-derived cholesterol. Science 294, 1354–1357.

    Article  PubMed  CAS  Google Scholar 

  • McGeer P. L. and McGeer E. G. (2001) Inflammation, autotoxicity and Alzheimer disease. Neurobiol. Aging 22, 799–809.

    Article  PubMed  CAS  Google Scholar 

  • Meda L., Casatella M. A., Szendrei G. I., Otvos L. Jr., Baron P., Villalba M., et al. (1995) Activation of microglial cells by β-Amyloid protein and interferon-γ Nature 374, 647–650.

    Article  PubMed  CAS  Google Scholar 

  • Naidu A., Xu Q., Catalano R., and Cordell B. (2002) Secretion of apolipoprotein E by brain glia requires protein prenylation and is suppressed by statins. Brain Res. 958, 100–111.

    Article  PubMed  CAS  Google Scholar 

  • Naslund J., Haroutunian V., Mohs R., Davis K. L., Davies P., Greengard P., and Buxbaum J. D. (2000) Correlation between elevated levels of amyloid beta peptide in the brain and cognitive decline. JAMA 283, 1571–1577.

    Article  PubMed  CAS  Google Scholar 

  • Neuroinflammation Working Group (2000) Inflammation and Alzheimer’s disease. Neurobiol. Aging 21, 383–421.

    Article  Google Scholar 

  • Notkola I. L., Sulkava R., Pekkanen J., Erkinjuntti T., Ehnholm C., Kivinen P., et al. (1998) Serum cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer’s disease. Neuroepidemiology 17, 14–20.

    Article  PubMed  CAS  Google Scholar 

  • Ordovas J. M. and Mooser V. (2002) The ApoE locus and the pharmacogenetics of lipid response. Curr. Opin. Lipidol. 13, 113–117.

    Article  PubMed  CAS  Google Scholar 

  • Papassotiropoulos A., Streffer J. R., Tsolaki M., et al. (2003) Increased brain beta-amyloid load, phosphorylated tau, and risk of Alzheimer disease associated with an intronic CYP46 polymorphism. Arch. Neurol. 60, 29–35.

    Article  PubMed  Google Scholar 

  • Parvathy S., Davies P., Haroutunian V., Purohit D. P., Davis K. L., Mohs R. C., et al. (2001) Correlation between Abeta x-40, Abeta x-42, and Abeta x-43 containing amyloid plaques and cognitive decline. Arch. Neurol. 58, 2025–2032.

    Article  PubMed  CAS  Google Scholar 

  • Petanceska S. S., DeRosa S., Olm V., et al. (2002) Statin therapy for Alzheimer’s disease: will it work? J. Mol. Neurosci. 19, 155–161.

    Article  PubMed  CAS  Google Scholar 

  • Petanceska S., Canoll P., and Devi L. A. (1996) Expression of rat cathepsin S in phagocytic cells. J. Biol. Chem. 271, 4403–4409.

    Google Scholar 

  • Prince M., Lovestone S., Cervilla J., Joels S., Powell J., Russ C., and Mann A. (2000) The association between ApoE and dementia does not seem to be mediated by vascular factors. Neurology 54, 397–402.

    PubMed  CAS  Google Scholar 

  • Poirier J. (2000) Apolipoprotein E and Alzheimer’s disease. A role in amyloid catabolism. Ann. N. Y. Acad. Sci. 924, 81–90.

    Article  PubMed  CAS  Google Scholar 

  • Puglielli L., Konopka G., Pack-Chung E., et al. (2001) Acylcoenzyme A: cholesterol acyl transferase modulates the generation of the amyloid beta-peptide. Nat. Cell. Biol. 3, 905–912.

    Article  PubMed  CAS  Google Scholar 

  • Refolo L. M., Malester B., LaFrancois J., Bryant-Thomas T., Wang R., Tint G. S., et al. (2000) Hypercholesterolemia accelerates the Alzheimer’s amyloid pathology in a transgenic mouse model. Neurobiol. Dis. 7, 321–331.

    Article  PubMed  CAS  Google Scholar 

  • Refolo L. M., Pappolla M. A., LaFrancois J., Malester B., Schmidt S. D., Thomas-Bryant T., et al. (2001) A cholesterol-lowering drug reduces beta-amyloid pathology in a transgenic mouse model of Alzheimer’s disease. Neurobiol. Dis. 8, 890–899.

    Article  PubMed  CAS  Google Scholar 

  • Rockwood K., Kirkland S., Hogan D. B., MacKnight, Merry H., Verreault R., et al. (2002) Use of lipid lowering agents, indication bias, and the risk of dementia in community dwelling elderly people. Arch. Neurol. 59, 223–227.

    Article  PubMed  Google Scholar 

  • Romas S. N., Tang M. X., Berglund L., and Mayeux R. (1999) APOE genotype, plasma lipids, lipoproteins, and AD in community elderly. Neurology 53, 517–521.

    PubMed  CAS  Google Scholar 

  • Runz H., Rietdorf J., Tomic I., et al. (2002) Inhibition of intracellular cholesterol transport alters presenilin localization and amyloid precursor protein processing in neuronal cells. J. Neurosci. 22, 1679–1689.

    PubMed  CAS  Google Scholar 

  • Santillo M., Migliaro A., Mondola P., Laezza C., Damiano S., Stingo S., et al. (1999) Dietary and hypothyroid hypercholesterolemia induces hepatic apolipoprotein E expression in the rat: direct role of cholesterol. FEBS Lett. 463, 83–86.

    Article  PubMed  CAS  Google Scholar 

  • Shie F. S., Jin L. W., Cook D. G., Leverenz J. B., and LeBoeuf R. C. (2002) Diet-induced hypercholesterolemia enhances brain A beta accumulation in transgenic mice. Neuroreport 13, 455–459.

    Article  PubMed  CAS  Google Scholar 

  • Simons M., Schwarzler F., Lutjohann D., von Bergmann C., Beyreuther K., Dichgans J., et al. (2002) Treatment with simvastatin in normocholesterolemic patients with Alzheimer’s disease: a 26 week randomized, placebo-controlled, double-blind trial. Ann. Neurol. 52, 346–350.

    Article  PubMed  CAS  Google Scholar 

  • Sparks D. L. (1996) Intraneuronal beta-amyloid immunoreactivity in the CNS. Neurobiol. Aging 17, 29,120–29,129.

    Google Scholar 

  • Sparks D. L., Liu H., Gross D. R., and Scheff S. W. (1995) Increased density of cortical apolipoprotein E immunoreactive neurons in rabbit brain after dietary administration of cholesterol. Neurosci. Lett. 187, 142–144.

    Article  PubMed  CAS  Google Scholar 

  • Srivastava R. (1996a) Regulation of the apolipoprotein E by dietary lipids occurs by transcriptional and post-transcriptional mechanisms. Mol. Cell. Sci. 155, 153–162.

    Google Scholar 

  • Srivastava R. A., Bhasin N., and Srivastava N. (1996b) Apolipoprotein E gene expression in various tissues of mouse and regulation by estrogen. Biochem. Mol. Biol. Intern. 38, 91–101.

    Google Scholar 

  • Stone D. J., Rozovsky I., Morgan T. E., Anderson C. P., Hajian H., and Finch C. E. (1997) Astrocytes and microglia respond to estrogen with increased ApoE mRNA in vivo and in vitro. Exp. Neurol. 143, 313–318.

    Article  PubMed  CAS  Google Scholar 

  • Wahrle S., Das P., Nyborg A. C., McLendon C., et al. (2002) Cholesterol-dependent gamma-secretase activity in buoyant cholesterol-rich membrane microdomains. Neurobiol. Dis. 9, 11–23.

    Article  PubMed  CAS  Google Scholar 

  • Wang J. C., Kwon J. M., and Shah P. (2000) Effect of APOE genotype and promoter polymorphism on risk of Alzheimer’s disease. Neurology 55, 1644–1649.

    PubMed  CAS  Google Scholar 

  • Werb Z. and Chin J. R. (1983) Endotoxin suppresses expression of apolipoprotein E by mouse macrophages in vivo and in culture. A biochemical and genetic study. J. Biol. Chem. 258, 10,642–10,648.

    CAS  Google Scholar 

  • Wolozin B., Kellman W., Ruosseau P., Celesia G. G., and Siegel G. (2000) Decreased prevalence of Alzheimer’s disease associated with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Arch. Neurol. 57, 1439–1443.

    Article  PubMed  CAS  Google Scholar 

  • Wong L. and Rubenstein D. (1997) The levels of apolipoprotein in hypercholesterolemic rat serum. J. Biochem. 56, 161–166.

    Google Scholar 

  • Yaffe K., Barrett-Connor E., Lin F., and Grady D. (2002) Serum lipoprotein levels, statin use, and cognitive function in older women. Arch. Neurol. 59, 378–384.

    Article  PubMed  Google Scholar 

  • Yoshitake T., Kiyohara Y., Kato I., Ohmura T., Iwamoto H., Nakayama K., et al. (1995) Incidence and risk factors of vascular dementia and Alzheimer’s disease in a defined elderly Japanese population: the Hisayama Study. Neurology 6, 1161–1168.

    Google Scholar 

  • Xu Q., Li Y., Cyras C., Sanan D. A., and Cordell B. (2000) Isolation and characterization of apolipoproteins from murine microglia. Identification of a low density lipoprotein-like apolipoprotein J-rich but E-poor spherical particle. J. Biol. Chem. 275, 31,770–31,777.

    CAS  Google Scholar 

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Authors and Affiliations

  1. Center for Dementia Research, Nathan Kline Institute, 10962, Orangeburg, NY

    Suzana S. Petanceska, Steven DeRosa, Ali Sharma, Nichole Diaz & Karen Duff

  2. Department of Psychiatry, NYU Medical Center, 10016, New York, NY

    Suzana S. Petanceska & Karen Duff

  3. University of Medicine and Dentistry of New Jersey, 08901, NJ

    Steven G. Tint

  4. Institute for the Study of Aging, 10153, New York, NY

    Lorenzo M. Refolo

  5. University of South Alabama, 36688, Mobile, AL

    Miguel Pappolla

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  1. Suzana S. Petanceska
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Correspondence to Suzana S. Petanceska.

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Petanceska, S.S., DeRosa, S., Sharma, A. et al. Changes in apolipoprotein E expression in response to dietary and pharmacological modulation of cholesterol. J Mol Neurosci 20, 395–406 (2003). https://doi.org/10.1385/JMN:20:3:395

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