Isoform-specific effects of apolipoprotein E on secretion of inflammatory mediators in adult rat microglia

Journal of Alzheimer's Disease

Volumn 7, Issue 1, 2005, Pages 25-35

  Chen, Shuang ^a,c   Averett, Natale T ^a   Manelli, Arlene ^b   LaDu, Mary Jo ^b   May, Warren ^a   Ard, March D ^a  

^a UNIVERSITY OF MISSISSIPPI MEDICAL CENTER   (United States)

^b ENH Research Institute   (United States)

^c HENRY FORD HOSPITAL   (United States)

Author keywords

ApoE4; Inflammation; Interleukin; Microglia; Neuroinflammation; Prostaglandin

Indexed keywords

APOLIPOPROTEIN E; APOLIPOPROTEIN E4; CYCLOOXYGENASE 2; INTERLEUKIN 1BETA; ISOPROTEIN; PROSTAGLANDIN E; PROSTAGLANDIN E2;

ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BRAIN CORTEX; CONTROLLED STUDY; DISEASE SEVERITY; GENETIC CODE; GENETIC CORRELATION; GENETIC RISK; INFLAMMATORY INFILTRATE; MICROGLIA; NONHUMAN; ONSET AGE; PRIORITY JOURNAL; PROSTAGLANDIN RELEASE; PROTEIN EXPRESSION; RAT; UPREGULATION;

EID: 15244340085     PISSN: 13872877     EISSN: None     Source Type: Journal    
DOI: 10.3233/JAD-2005-7104     Document Type: Article

References (85)

1. H. Akiyama, S. Barger, S. Barnum, B. Bradt, J. Bauer, G.M. Cole, N.R. Cooper, P. Eikelenboom, M. Emmerling, B.L. Fiebich, C.E. Finch, S. Frautschy, W.S. Griffin, H. Hampel, M. Hull, G. Landreth, L. Lue, R. Mrak, I.R. Mackenzie, P.L. McGeer, M.K. O'Banion, J. Pachter, G. Pasinetti, C. Plata-Salaman, J. Rogers, R. Rydel, Y. Shen, W. Streit, R. Strohmeyer, I. Tooyoma, F.L. Van Muiswinkel, R. Veerhuis, D. Walker, S. Webster, B. Wegrzyniak, G. Wenk and T. Wyss-Coray, Inflammation and Alzheimer's disease, Neurobiology of Aging 21 (2000), 383-421.
2. S.M. Albert, B. Gurland, G. Maestre, D.M. Jacobs, Y. Stern and R. Mayeux, APOE genotype influences functional status among elderly without dementia, American Journal of Medical Genetics 60 (1995), 583-587.
3. S.M. Allan and N.J. Rothwell, Cytokines and acute neurodegeneration, Nature Review of Neuroscience 2 (2001), 734-744.
4. K. Andersen, L.J. Launer, A. Ott, A.W. Hoes, M.M. Breteler and A. Hofman, Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer's disease? The Rotterdam Study, Neurology 45 (1995), 1441-1445.
5. 2 receptor antagonists: the Cache County study, Neurology 54 (2000), 2066-2071.
6. M.D. Ard, G.M. Cole, J. Wei, A.P. Mehrle and J.D. Fratkin, Scavenging of Alzheimer's amyloid beta-protein by microglia in culture, Journal of Neuroscience Research 43 (1996), 190-202.
7. S.W. Barger and A.D. Harmon, Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E, Nature 388 (1997), 878-881.
8. K.G. Becker, APOE genotype is a major predictor of long-term progression of disability in MS, Neurology 57 (2001), 2148-2149.
9. P. Bertrand, J. Poirier, T. Oda, C.E. Finch and G.M. Pasinetti, Association of apolipoprotein E genotype with brain levels of apolipoprotein E and apolipoprotein J (clusterin) in Alzheimer disease, Brian Research: Molecular Brain Research 33 (1995), 174-178.
10. P. Bezzi, M. Domercq, L. Brambilla, R. Galli, D. Schols, E. De Clercq, A. Vescovi, G. Bagetta, G. Kollias, J. Meldolesi and A. Volterra, CXCR4-activated astrocyte glutamate release via TNFalpha: amplification by microglia triggers neurotoxicity, Nature Neuroscience 4 (2001), 702-710.
11. J.E. Bottenstein, Culture methods for growth of neuronal cell lines in defined media, in: Methods for serum-free culture of neuronal and lymphoid cells, D.W. Barnes, D.A. Sirbasku and G.H. Sato, eds, Alan R Liss, New York, 1984, pp. 3-13.
12. J.K. Boyles, R.E. Pitas, E. Wilson, R.W. Mahley and J.M. Taylor, Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system, Journal of Clinical Investigation 76 (1985), 1501-1513.
13. J.C. Breitner, B.A. Gau, K.A. Welsh, B.L. Plassman, W.M. McDonald, M.J. Helms and J.C. Anthony, Inverse association of anti-inflammatory treatments and Alzheimer's disease: initial results of a co-twin control study, Neurology 44 (1994), 227-232.
14. J.C. Breitner, G.P. Jarvik, B.L. Plassman, A.M. Saunders and K. A. Welsh, Risk of Alzheimer disease with the epsilon4 allele for apolipoprotein E in a population-based study of men aged 62-73 years, Alzheimer Disease and Associated Disorders 12 (1998), 40-44.
15. J.C. Breitner, K.A. Welsh, M.J. Helms, P.C. Gaskell, B.A. Gau, A.D. Roses, M.A. Pericak-Vance and A.M. Saunders, Delayed onset of Alzheimer's disease with nonsteroidal anti-inflammatory and histamine H2 blocking drugs, Neurobiology of Aging 16 (1995), 523-530.
16. T.W. Briers, C. Desmaretz and E. Vanmechelen, Generation and characterization of mouse microglial cell lines, Journal of Neuroimmunology 52 (1994), 153-164.
17. C.M. Brown, E. Wright, C.A. Colton, P.M. Sullivan, D.T. Laskowitz and M.P. Vitek, Apolipoprotein E isoform mediated regulation of nitric oxide release, Free Radical Biology and Medicine 32 (2002), 1071-1075.
18. J. Chapman, A.D. Korczyn, D.M. Karussis and D.M. Michaelson, The effects of APOE genotype on age at onset and progression of neurodegenerative diseases, Neurology 57 (2001), 1482-1485.
19. R.H. Christie, H. Chung, G.W. Rebeck, D. Strickland and B.T. Hyman, Expression of the very low-density lipoprotein receptor (VLDL-r), an apolipoprotein-E receptor, in the central nervous system and in Alzheimer's disease, Journal of Neuropathology and Experimental Neurology 55 (1996), 491-498.
20. G.M. Cole, W. Beech, S.A. Frautschy, J. Sigel, C. Glasgow and M.D. Ard, Lipoprotein effects on Abeta accumulation and degradation by microglia in vitro, Journal of Neuroscience Research 57 (1999), 504-520.
21. C.A. Colton, C.M. Brown, D. Cook, L.K. Needham, Q. Xu, M. Czapiga, A.M. Saunders, D.E. Schmechel, K. Rasheed and M.P. Vitek, APOE and the regulation of microglial nitric oxide production: a link between genetic risk and oxidative stress, Neurobiology of Aging 23 (2002), 777.
22. D.W. Dickson, S.C. Lee, L.A. Mattiace, S.H. Yen and C. Brosnan, Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer's disease, Glia 7 (1993), 75-83.
23. V.E. Drory, M. Birnbaum, A.D. Korczyn and J. Chapman, Association of APOE epsilon4 allele with survival in amyotrophic lateral sclerosis, Journal of the Neurological Sciences 190 (2001), 17-20.
24. R. Egensperger, S. Kosel, U. von Eitzen and M.B. Graeber, Microglial activation in Alzheimer disease: Association with APOE genotype, Brain Pathology 8 (1998), 439-447.
25. C. Enzinger, S. Ropele, S. Strasser-Fuchs, P. Kapeller, H. Schmidt, B. Poltrum, R. Schmidt, H.P. Hartung and F. Fazekas, Lower levels of N-acetylaspartate in multiple sclerosis patients with the apolipoprotein E epsilon4 allele, Archives of Neurology 60 (2003), 65-70.
26. A.M. Fagan, D.M. Holtzman, G. Munson, T. Mathur, D. Schneider, L.K. Chang, G.S. Getz, C.A. Reardon, J. Lukens, J.A. Shah and M.J. LaDu, Unique lipoproteins secreted by primary astrocytes from wild type, apoE (-/-), and human apoE transgenic mice, Journal of Biological Chemistry 274 (1999), 30001-30007.
27. F. Fazekas, S. Strasser-Fuchs, H. Kollegger, T. Berger, W. Kristoferitsch, H. Schmidt, C. Enzinger, M. Schiefermeier, C. Schwarz, B. Kornek, M. Reindl, K. Huber, R. Grass, G. Wimmer, K. Vass, K.H. Pfeiffer, H.P. Hartung and R. Schmidt, Apolipoprotein E epsilon 4 is associated with rapid progression of multiple sclerosis, Neurology 57 (2001), 853-857.
28. G. Friedman, P. Froom, L. Sazbon, I. Grinblatt, M. Shochina, J. Tsenter, S. Babaey, B. Yehuda and Z. Groswasser, Apolipoprotein E-epsilon4 genotype predicts a poor outcome in survivors of traumatic brain injury, Neurology 52 (1999), 244-248.
29. D. Giulian and T.J. Baker, Characterization of ameboid microglia isolated from developing mammalian brain, Journal of Neuroscience 6 (1986), 2163-2178.
30. W.S. Griffin, J.G. Sheng, G.W. Roberts and R.E. Mrak, Interleukin-1 expression in different plaque types in Alzheimer's disease: significance in plaque evolution, Journal of Neuropathology and Experimental Neurology 54 (1995), 276-281.
31. W.S. Griffin, L.C. Stanley, C. Ling, L. White, V. MacLeod, L.J. Perrot, C.L. White, 3rd and C. Araoz, Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease, Proceedings of the National Academy of Sciences USA 86 (1989), 7611-7615.
32. L. Guo, M.J. LaDu and L.J. Van Eldik, A dual role for apolipoprotein e in neuroinflammation: anti- and pro-inflammatory activity, Journal of Molecular Neuroscience 23 (2004), 205-212.
33. S.D. Harr, L. Uint, R. Hollister, B.T. Hyman and A.J. Mendez, Brain expression of apolipoproteins E, J, and A-I in Alzheimer's disease, Journal of Neurochemistry 66 (1996), 2429-2435.
34. W. Hartig, G. Bruckner, C. Schmidt, K. Brauer, G. Bodewitz, J.D. Turner and V. Bigl, Co-localization of beta-amyloid peptides, apolipoprotein E and glial markers in senile plaques in the prefrontal cortex of old rhesus monkeys, Brain Research 751 (1997), 315-322.
35. J. Herz, M. Gotthardt and T.E. Willnow, Cellular signalling by lipoprotein receptors, Current Opinion in Lipidology 11 (2000), 161-166.
36. C. Hesse, H. Larsson, P. Fredman, L. Minthon, N. Andreasen, P. Davidsson and K. Blennow, Measurement of apolipoprotein E (apoE) in cerebrospinal fluid, Neurochemical Research 25 (2000), 511-517.
37. J.J. Hoozemans, A.J. Rozemuller, I. Janssen, C.J. De Groot, R. Veerhuis and P. Eikelenboom, Cyclooxygenase expression in microglia and neurons in Alzheimer's disease and control brain, Acta Neuropathologica (Berlin) 101 (2001), 2-8.
38. J.J. Hoozemans, R. Veerhuis, I. Janssen, E.J. van Elk, A.J. Rozemuller and P. Eikelenboom, The role of cyclo-oxygenase 1 and 2 activity in prostaglandin E(2) secretion by cultured human adult microglia: implications for Alzheimer's disease, Brain Research 951 (2002), 218-226.
39. B.A. in' t Veld, A. Ruitenberg, A. Hofman, L.J. Launer, C.M. van Duijn, T. Stijnen, M.M. Breteler and B.H. Stricker, Non-steroidal antiinflammatory drugs and the risk of Alzheimer's disease, New England Joournal of Medicine 345 (2001), 1515-1521.
40. T.L. Innerarity and R.W. Mahley, Enhanced binding by cultured human fibroblasts of apo-E-containing lipoproteins as compared with low density lipoproteins, Biochemistry 17 (1978), 1440-1447.
41. T.L. Innerarity, R.E. Pitas and R.W. Mahley, Binding of arginine-rich (E) apoprotein after recombination with phospholipid vesicles to the low density lipoprotein receptors of fibroblasts, Journal of Biological Chemistry 254 (1979), 4186-4190.
42. T.L. Innerarity, R.E. Pitas and R.W. Mahley, Lipoprotein-receptor interactions, Methods in Enzymology 129 (1986), 542-565.
43. K. Ishii, A. Tamaoka, H. Mizusawa, S. Shoji, T. Ohtake, P.E. Fraser, H. Takahashi, S. Tsuji, M. Gearing, T. Mizutani, S. Yamada, M. Kato, P.H. St George-Hyslop, S.S. Mirra and H. Mori, Abeta1-40 but not Abeta1-42 levels in cortex correlate with apolipoprotein E epsilon4 allele dosage in sporadic Alzheimer's disease, Brain Research 748 (1997), 250-252.
44. B.D. Jordan, N.R. Relkin, L.D. Ravdin, A.R. Jacobs, A. Bennett and S. Gandy, Apolipoprotein E epsilon4 associated with chronic traumatic brain injury in boxing, Journal of the American Medical Association 278 (1997), 136-140.
45. A.R. Koudinov, N.V. Koudinova, A. Kumar, R.C. Beavis and J. Ghiso, Biochemical characterization of Alzheimer's soluble amyloid beta protein in human cerebrospinal fluid: association with high density lipoproteins, Biochemical and Biophysical Research Communications 223 (1996), 592-597.
46. M.J. LaDu, S.M. Gilligan, J.R. Lukens, V.G. Cabana, C.A. Reardon, L.J. Van Eldik and D.M. Holtzman, Nascent astrocyte particles differ from lipoproteins in CSF, Journal of Neurochemistry 70 (1998), 2070-2081.
47. Y. Li, J. Cam and G. Bu, Low-density lipoprotein receptor family: endocytosis and signal transduction, Molecular Neurobiology 23 (2001), 53-67.
48. V.R. Lombardi, M. Garcia and R. Cacabelos, Microglial activation induced by factor(s) contained in sera from Alzheimer-related ApoE genotypes, Journal of Neuroscience Research 54 (1998), 539-553.
49. U. Lucca, M. Tettamanti, G. Forloni and A. Spagnoli, Non-steroidal antiinflammatory drug use in Alzheimer's disease, Biological Psychiatry 36 (1994), 854-856.
50. R.W. Mahley, Apolipoprotein E: cholesterol transport protein with expanding role in cell biology, Science 240 (1988), 622-630.
51. R.W. Mahley and Y. Huang, Apolipoprotein E: from atherosclerosis to Alzheimer's disease and beyond, Current Opinion in Lipidology 10 (1999), 207-217.
52. M.P. Marzolo, R. von Bernhardi, G. Bu and N.C. Inestrosa, Expression of alpha(2)-macroglobulin receptor/low density lipoprotein receptor-related protein (LRP) in rat microglial cells, Journal of Neuroscience Research 60 (2000), 401-411.
53. M.O. McCarron, K.L. Hoffmann, D.M. DeLong, L. Gray, A.M. Saunders and M.J. Alberts, Intracerebral hemorrhage outcome: apolipoprotein E genotype, hematoma, and edema volumes, Neurology 53 (1999), 2176-2179.
54. P.L. McGeer, E. McGeer, J. Rogers and J. Sibley, Anti-inflammatory drugs and Alzheimer disease, Lancet 335 (1990), 1037.
55. M.J. McNamara, T. Gomez-Isla and B.T. Hyman, Apolipoprotein E genotype and deposits of Abeta40 and Abeta42 in Alzheimer disease, Archives of Neurology 55 (1998), 1001-1004.
56. G.S. Merz, V. Schwenk, G. Schuller-Levis, S. Gruca and H.M. Wisniewski, Isolation and characterization of macrophages from scrapie-infected mouse brain, Acta Neuropathologica (Berlin) 72 (1987), 240-247.
57. A. Michler-Stuke, J.R. Wolff and J.E. Bottenstein, Factors influencing astrocyte growth and development in defined media, International Journal of Developmental Neuroscience 2 (1984), 575-584.
58. J.A. Mitchell, P. Akarasereenont, C. Thiemermann, R.J. Flower and J.R. Vane, Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase, Proceedings of the National Academy of Sciences USA 90 (1993), 11693-11697.
59. T.J. Montine, K.R. Sidell, B.C. Crews, W.R. Markesbery, L.J. Marnett, L.J. Roberts and J.D. Morrow, Elevated CSF prostaglandin E2 levels in patients with probable AD, Neurology 53 (1999), 1495-1498.
60. B. Moulard, A. Sefiani, A. Laamri, A. Malafosse and W. Camu, Apolipoprotein E genotyping in sporadic amyotrophic lateral sclerosis: evidence for a major influence on the clinical presentation and prognosis, Journal of the Neurological Sciences 139(Suppl) (1996), 34-37.
61. M. Nakai, T. Kawamata, T. Taniguchi, K. Maeda and C. Tanaka, Expression of apolipoprotein E mRNA in rat microglia, Neuroscience Letters 211 (1996), 41-44.
62. M. Narita, D.M. Holtzman, A.M. Fagan, M.J. LaDu, L. Yu, X. Han, R.W. Gross, G. Bu and A.L. Schwartz, Cellular catabolism of lipid poor apolipoprotein E via cell surface LDL receptor-related protein, Journal of Biochemistry (Tokyo) 132 (2002), 743-749.
63. T.G. Ohm, H. Scharnagl, W. Marz and J. Bohl, Apolipoprotein E isoforms and the development of low and high Braak stages of Alzheimer's disease-related lesions, Acta Neuropathologica (Berlin) 98 (1999), 273-280.
64. R.E. Pitas, J.K. Boyles, S.H. Lee, D. Foss and R.W. Mahley, Astrocytes synthesize apolipoprotein E and metabolize apolipoprotein E-containing lipoproteins, Biochimica et Biophysica Acta 917 (1987), 148-161.
65. J. Poirier, Apolipoprotein E and Alzheimer's disease. A role in amyloid catabolism, Annals of the New York Academy of Sciences 924 (2000), 81-90.
66. J. Poirier, J. Davignon, D. Bouthillier, S. Kogan, P. Bertrand and S. Gauthier, Apolipoprotein E polymorphism and Alzheimer's disease, Lancet 342 (1993), 697-699.
67. G.W. Rebeck, J.S. Reiter, D.K. Strickland and B.T. Hyman, Apolipoprotein E in sporadic Alzheimer's disease: allelic variation and receptor interactions, Neuron 11 (1993), 575-580.
68. J.B. Rich, D.X. Rasmusson, M.F. Folstein, K.A. Carson, C. Kawas and J. Brandt, Nonsteroidal anti-inflammatory drugs in Alzheimer's disease, Neurology 45 (1995), 51-55.
69. J. Rogers, L.C. Kirby, S.R. Hempelman, D.L. Berry, P.L. McGeer, A.W. Kaszniak, J. Zalinski, M. Cofield, L. Mansukhani and P. Willson, Clinical trial of indomethacin in Alzheimer's disease, Neurology 43 (1993), 1609-1611.
70. J. Rogers, S. Webster, L.F. Lue, L. Brachova, W.H. Civin, M. Emmerling, B. Shivers, D. Walker and P. McGeer, Inflammation and Alzheimer's disease pathogenesis, Neurobiology of Aging 17 (1996), 681-686.
71. C. Russo, G. Angelini, D. Dapino, A. Piccini, G. Piombo, G. Schettini, S. Chen, J.K. Teller, D. Zaccheo, P. Gambetti and M. Tabaton, Opposite roles of apolipoprotein E in normal brains and in Alzheimer's disease, Proceedings of the National Academy of Sciences USA 95 (1998), 15598-15602.
72. A.M. Saunders, Apolipoprotein E and Alzheimer disease: an update on genetic and functional analyses, Journal of Neuropathology and Experimental Neurology 59 (2000), 751-758.
73. A.M. Saunders, W.J. Strittmatter, D. Schmechel, P.H. George-Hyslop, M.A. Pericak-Vance, S.H. Joo, B.L. Rosi, J.F. Gusella, D.R. Crapper-MacLachlan, M.J. Alberts, C.M. Hulette, B.J. Crain, D. Goldgaber and A.D. Roses, Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease, Neurology 43 (1993), 1467-1472.
74. D.E. Schmechel, A.M. Saunders, W.J. Strittmatter, B.J. Grain, C.M. Hulette, S.H. Joo, M.A. Pericak-Vance, D. Goldgaber and A.D. Roses, Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease, Proceedings of the National Academy of Sciences USA 90 (1993), 9649-9653.
75. J.G. Sheng, R.E. Mrak and W.S. Griffin, Glial-neuronal interactions in Alzheimer disease: progressive association of IL-1alpha+ microglia and S100beta+ astrocytes with neurofibrillary tangle stages, Journal of Neuropathology and Experimental Neurology 56 (1997), 285-290.
76. G. Siest, P. Bertrand, B. Qin, B. Herbeth, J.M. Serot, L. Masana, J. Ribalta, A.P. Passmore, A. Evans, M. Ferrari, M. Franceschi, J. Shepherd, M. Cuchel, U. Beisiegel, K. Zuchowsky, A.S. Rukavina, J. Sertic, M. Stojanov, V. Kostic, A. Mitrevski, V. Petrova, C. Sass, A. Merched, J.T. Salonen, L. Tiret and S. Visvikis, Apolipoprotein E polymorphism and serum concentration in Alzheimer's disease in nine European centres: the ApoEurope study. ApoEurope group, Clinical Chemistry and Laboratory Medicine 38 (2000), 721-730.
77. N. Slepko and G. Levi, Progressive activation of adult microglial cells in vitro, Glia 16 (1996), 241-246.
78. S. Sorbi, B. Nacmias, S. Piacentini, A. Repice, S. Latorraca, P. Forleo and L. Amaducci, ApoE as a prognostic factor for post-traumatic coma, Nature Medicine 1 (1995), 852.
79. W.F. Stewart, C. Kawas, M. Corrada and E.J. Metter, Risk of Alzheimer's disease and duration of NSAID use, Neurology 48 (1997), 626-632.
80. D.J. Stone, I. Rozovsky, T.E. Morgan, C.P. Anderson, H. Hajian and C.E. Finch, Astrocytes and microglia respond to estrogen with increased apoE mRNA in vivo and in vitro, Experimental Neurology 143 (1997), 313-318.
81. W.J. Strittmatter, A.M. Saunders, D. Schmechel, M. Pericak-Vance, J. Enghild, G.S. Salvesen and A.D. Roses, Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease, Proceedings of the National Academy of Sciences USA 90 (1993), 1977-1981.
82. G.M. Teasdale, J.A. Nicoll, G. Murray and M. Fiddes, Association of apolipoprotein E polymorphism with outcome after head injury, Lancet 350 (1997), 1069-1071.
83. J.R. Vane, Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs, Nature New Biology 231 (1971), 232-235.
84. D. Woo, L.R. Sauerbeck, B.M. Kissela, J.C. Khoury, J.P. Szaflarski, J. Gebel, R. Shukla, A.M. Pancioli, E.C. Jauch, A.G. Menon, R. Deka, J.A. Carrozzella, C.J. Moomaw, R.N. Fontaine and J.P. Broderick, Genetic and environmental risk factors for intracerebral hemorrhage: preliminary results of a population-based study, Stroke 33 (2002), 1190-1195; discussion 1195-1196.
85. A.V. Yermakova, J. Rollins, L.M. Callahan, J. Rogers and M.K. O'Banion, Cyclooxygenase-1 in human Alzheimer and control brain: quantitative analysis of expression by microglia and CA3 hippocampal neurons, Journal of Neuropathology and Experimental Neurology 58 (1999), 1135-1146.