Impaired regulation of immune responses in cognitive decline and Alzheimer's disease: Lessons from genetic association studies

Expert Review of Neurotherapeutics

Volumn 6, Issue 9, 2006, Pages 1327-1336

  Chiappelli, Martina ^a   Tumini, Emanuela ^a   Porcellini, Elisa ^a   Licastro, Federico ^a  

^a UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

Alzheimer's disease risk; Anti inflammatory treatments; Disease progression; Gene polymorphisms; Gene risk profile; Inflammatory molecules

Indexed keywords

ALPHA 1 ANTICHYMOTRYPSIN; CYTOKINE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE; INTERLEUKIN 1; INTERLEUKIN 10; INTERLEUKIN 6; NONSTEROID ANTIINFLAMMATORY AGENT; SERINE PROTEINASE INHIBITOR; TUMOR NECROSIS FACTOR ALPHA;

ALZHEIMER DISEASE; ASTROCYTOSIS; BRAIN CELL; CLINICAL TRIAL; COGNITIVE DEFECT; CONFIDENCE INTERVAL; DISEASE COURSE; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; GENETIC VARIABILITY; GENOTYPE; HUMAN; IMMUNE RESPONSE; META ANALYSIS; MICROGLIA; NERVE DEGENERATION; PATHOGENESIS; REVIEW; RISK FACTOR; SENILE DEMENTIA; SYSTEMATIC REVIEW; UPREGULATION;

ALZHEIMER DISEASE; CLINICAL TRIALS; COGNITION DISORDERS; GENETIC PREDISPOSITION TO DISEASE; HLA-D ANTIGENS; HUMANS; IMMUNOLOGIC FACTORS;

EID: 33750035496     PISSN: 14737175     EISSN: 17448360     Source Type: Journal    
DOI: 10.1586/14737175.6.9.1327     Document Type: Review

References (108)

1. Aronson MK, Ooi WL, Geva DL, Masur D, Blau A, Frishman W. Dementia. Age-dependent incidence, prevalence, and mortality in the old old. Arch. Intern. Med. 151(5), 989-992 (1991).
2. Terry RD. Neuropathological changes in Alzheimer's disease. Prog. Brain Res. 101, 383-390 (1994).
3. Trojanowski JQ, Clark CM, Schmidt ML, Arnold SE, Lee VM. Strategies for improving the postmortem neuropathological diagnosis of Alzheimer's disease. Neurobiol. Aging 18(Suppl. 4), S75-S79 (1997).
4. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 34(7), 939-944 (1984).
5. Breteler MMB, Claus JJ, van Duijn CM et al. Epidemiology of Alzheimer's disease. Epidemiol. Rev. 14, 59-82 (1992).
6. Dickson DW, Farlo J, Davies P, Crystal H, Fuld P, Yen SH. Alzheimer's disease. A double-labeling immunohistochemical study of senile plaques. Am. J. Pathol. 132, 86-101 (1988).
7. Rogers J, Luber-Narod J, Styren SD, Civin WH. Expression of immune system-associated antigens by cells of the human central nervous system: relationship to the pathology of Alzheimer's disease. Neurobiol. Aging 9, 339-349 (1988).
8. McGeer PL, Schulzer M, McGeer EG. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: a review of 17 epidemiologic studies. Neurology 47(2), 425-432 (1996). • Suggests a pathogenetic association of inflammation with Alzheimer's disease (AD).
9. Breitner JC, Gau BA, Welsh KA et al. Inverse association of anti-inflammatory treatments and Alzheimer's disease: initial results of a co-twin control study. Neurology 44, 227-232 (1994).
10. Landi F, Cesari M, Onder G, Russo A, Torre S, Bernabei R. Non steroidal antiinflammatory drug (NSAID) use and Alzheiemer's disease in community-dwelling elderly patients. Am. J. Geriatr. Psychiatry 11(2), 179-185 (2003)
11. Lindsay J, Laurin D, Verreault R et al. Risk factor for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging. Am. J. Epidemiol. 156(5), 445-453 (2002).
12. In t' Veld BA, Ruitenberg A, Hofman A et al. Nonsteroidal anti-inflammatory drugs and the risk of Alzheimer's disease. N. Engl. J. Med. 345(21), 1515-1521 (2001).
13. Licastro F, Pedrini S, Caputo L et al. Increased plasma levels of interleukin-1, interleukin-6 and α-1-antichymotrypsin in patients with Alzheimer's disease: peripheral inflammation or signals from the brain? J. Neuroimmunol. 103(1), 97-102 (2000). • First paper suggesting an atypical form of inflammation in AD.
14. Mancardi GL, Liwnicz BH, Mandybur TI. Fibrous astrocytes in Alzheimer's disease and senile dementia of Alzheimer's type. Acta. Neurophathol. (Berl.) 61, 76-80 (1983).
15. GriffinWS, Stanley LC, Ling C et al. Brain interleukin-1 and S-100 immunoreactivity are elevated in Down's syndrome and Alzheimer's disease. Proc. Natl Acad. Sci. USA 86, 7611-7615 (1989).
16. Bauer J, Ganter U, Strauss S et al. The participation of interleukin-6 in the pathogenesis of Alzheimer's disease. Res. Immunol. 143, 650-657 (1992).
17. Sawada M, Kondo N, Suzumura A, Marunouchi T. Production of tumor necrosis factor-α by microglia and astrocytes in culture. Brain Res. 491, 394-397 (1989).
18. Abraham CR, Selkoe DJ, Potter H. Immunochemical identification of the serine protease inhibitor, α-1-antichymotrypsin in the brain amyloid deposits. Cell 52, 487-501 (1988).
19. Goldgaber D, Harris HW, Hla T et al. Interleukin-1 regulates syntesis of amyloid β-protein precursor mRNA in human endothelial cells. Proc. Natl Acad. Sci. USA 86, 7606 (1989).
20. Selkoe DJ. Amyloid beta protein precursor and the pathogenesis of Alzheimer's disease. Cell 58, 611 (1989).
21. McGeer PL, Kawamata T, Walker DG, Akiyama H, Tooyama I, McGeer EG. Microglia in degenerative neurological disease. Glia 7, 84-92 (1993).
22. Rozemuller JM, Eikelenboom P, Pals ST, Stam FC. Microglial cells around amyloid plaques in Alzheimer's disease express leukocyte adhesion molecules of the LFA-1 family. Neurosci. Lett. 101, 288-292 (1989).
23. Canning DR, McKeon RJ, DeWitt DA et al. Beta-amyloid of Alzheimer's disease induces reactive gliosis that inhibits axonal outgrowth. Exp. Neurol. 124, 289-298 (1993).
24. Hoke A, Canning DR, Malemud CJ, Silver J. Regional difference in reactive gliosis induced by substrate-bound β-amyloid. Exp. Neurol. 130, 56-66 (1994).
25. Griffin WS, Sheng JG, Royston MC et al. Glial-neuronal interactions in Alzheimer's disease: the potential role of a 'cytokine cycle' in disease progression. Brain Pathol. 8(1), 65-72 (1998).
26. Mrak RE, Sheng JG, Griffin WS. Glial cytokines in Alzheimer's disease: review and pathogenic implications. Hum. Pathol. 26(8), 816-823 (1995).
27. Kelso A. Cytokines: principles and prospect. Immunol. Cell Biol. 76, 300-317 (1998).
28. Frei K, Malipiero UV, Leist TP, Zinkernagel RM, Schwab ME, Fontana A. On the cellular source and function of interleukin 6 produced in the central nervous system in viral diseases. Eur. J. Immunol. 19(4), 689-694 (1989).
29. Griffin WS, Sheng JG, Roberts GW, Mrak RE. Interleukin-1 expression in different plaque types in Alzheimer's disease: significance in plaque evolution. J. Neuropathol. Exp. Neurol. 54(2), 276-281 (1995).
30. Tarkowski E, Blennow K, Wallin A, Tarkowski A. Intracerebral production of tumor necrosis factor-alpha, a local neuroprotective agent, in Alzheimer disease and vascular dementia. J. Clin. Immunol. 19(4), 223-230 (1999).
31. Rubinsztein DC. The genetics of Alzheimer's disease. Prog. Neurobiol. 52, 447-454 (1997).
32. Corder EH, Saunders AM, Strittmatter WJ et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 261, 921-923 (1993). • Seminal report showing apolipoprotein (APO)E association with AD risk.
33. Poirier J, Davignon J, Bouthillier D, Kogan S, Bertrand P, Gauthier S. Apolipoprotein E polymorphism and Alzheimer's disease. Lancet 342, 697-699 (1993).
34. McGeer PL, Rogers J, McGeer EG. Neuroimmune mechanisms in Alzheimer's disease pathogenesis. Alzheimer Dis. Assoc. Disord. 8, 149-158 (1994).
35. Dinarello CA. The interleukin-1 family: 10 years of discovery. FASEB J. 8, 1314-1325 (1994).
36. Mrak RE, Griffin WST. Interleukin-1 and the immunogenetics of Alzheimer's disease. J. Neurophatol. Exp. Neurol. 59, 471-476 (2000).
37. Buxbaum JD, Liu KN, Luo Y et al. Evidence that tumor necrosis factor alpha converting enzyme is involved in regulated α-secretase cleavage of the Alzheimer amyloid protein precursor. J. Biol. Chem. 273(43), 27765-27767 (1998).
38. Barger SW, Harmon AD. Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E. Nature 388(6645), 878-881 (1997).
39. Giulian D, Woodward J, Young DG, Krebs JF, Lachman LB. Interleukin-1 injected into mammalian brain stimulates astrogliosis and neovascularization. J. Neurosci. 8(7), 2485-2490 (1988).
40. Das S, Potter H. Expression of the Alzheimer amyloid-promoting factor antichymotrypsin is induced in human astrocytes by IL-1. Neuron 14(2), 447-456 (1995).
41. McGeer PL, Akiyama H, Itagaki S, McGeer EG. Activation of the classical complement pathway in brain tissue of Alzheimer patients. Neurosci. Lett. 107(1-3), 341-346 (1989).
42. Sheng JG, Ito K, Skinner RD, et al. In vivo and in vitro evidence supporting a role for the inflammatory cytokine interleukin-1 as a driving force in Alzheimer pathogenesis. Neurobiol. Aging 17(5), 761-766 (1996).
43. Nicoll JAR, Mrak RE, Graham DI et al. Association of interleukin-1 gene polymorphisms in Alzheimer's disease. Ann. Neurol. 47, 365-368 (2000). • First paper showing a genetic association of interleukin (IL)-1β with increased AD risk.
44. Combarros O, Sanchez-Guerra M, Infante J, Llorca J, Berciano J. Gene dose-dependent association of interleukin-1α (-889) allele 2 polymorphism with Alzheimer's disease. J. Neurol. 249(9), 1242-1245 (2002).
45. Grimaldi LME, Casadei VM, Ferri C et al. Association of early-onset Alzheimer's disease with an interleukin-1α gene polymorphism. Ann. Neurol. 47, 361-365 (2000). • First paper reporting a genetic association of IL-1α with increased risk of AD.
46. Rebeck GW. Confirmation of genetic association of interleukin-1A with early onset sporadic Alzheimer's disease. Neurosci. Lett. 293, 75-77 (2000).
47. Du Y, Dodel RC, Eastwood BJ et al. Association of an interleukin-1α polymorphism with Alzheimer's disease. Neurology 55, 480-483 (2000).
48. Hedley R, Hallmayer J, Groth DM, Brooks WS, Gandy SE, Martins RN. Association of interleukin-1 polymorphisms with Alzheimer's disease in Australia. Ann. Neurol. 51(6), 795-797 (2002).
49. Kuo YM, Liao PC, Lin C et al. Lack of association between interleukin-1α polymorphism and Alzheimer disease or vascular dementia. Alzheimer Dis. Assoc. Disord. 17(2), 94-97 (2003).
50. Pirskanen M, Hiltunen M, Mannermaa A et al. Interleukin 1 α gene polymorphism as a susceptibility factor in Alzheimer's disease and its influence on the extent of histopathological hallmark lesions of Alzheimer's disease. Dement. Geriatr. Cogn. Disord. 14(3), 123-127 (2002).
51. Green EK, Harris JM, Lemmon H et al. Are interleukin-1 gene polymorphisms risk factors or disease modifiers in AD? Neurology 58(10), 1566-1568 (2002).
52. Fidani L, Goulas A, Mirtsou V et al. Interleukin-1A polymorphism is not associated with late onset Alzheimer's disease. Neurosci. Lett. 323(1), 81-83 (2002).
53. Combarros O, Llorca J, Sanchez-Guerra M, Infante J, Berciano J. Age-dependent association between interleukin-1A (-889) genetic polymorphism and sporadic Alzheimer's disease. A meta-analysis. J. Neurol. 250(8), 987-989 (2003).
54. Sciacca FL, Ferri C, Licastro F et al. Interleukin-1B polymorphism is associated with age at onset of Alzheimer's disease. Neurobiol. Aging 24(7), 927-931 (2003)
55. Licastro F, Veglia F, Chiappelli M, Grimaldi LM, Masliah E. A polymorphism of the interleukin-1 β gene at position +3953 influences progression and neuropathological hallmarks of Alzheimer's disease. Neurobiol. Aging 25(8),1017-1022 (2004). • Important paper showing an influence of IL-β on AD progression.
56. Yucesoy B, Peila R, White LR et al. Association of interleukin-1 polymorphisms with dementia in a community-based sample: the Honolulu-Asia Aging Study. Neurobiol. Aging 27(2), 211-217 (2006).
57. Ehl C, Kolsch H, Ptok U et al. Association of an interleukin-1β polymorphism at position -511 with Alzheimer's disease. Int. J. Mol. Med. 11(2), 235-238 (2003).
58. Fagiolo U, Cossarizza A, Scala E et al. Increased cytokine production in mononuclear cells of elderly people. Eur. J. Immunol. 23, 2375-2378 (1993).
59. Marz P, Cheng JG, Gadient RA et al. Sympathetic neurons can produce and respond to interleukin 6. Proc. Natl Acad. Sci. USA 95(6), 3251-3256 (1998).
60. Van Wagoner NJ, Oh JW, Repovic P, Benveniste EN. Interleukin-6 (IL-6) production by astrocytes: autocrine regulation by IL-6 and the soluble IL-6 receptor. J. Neurosci. 19(13), 5236-5244 (1999)
61. Gadient RA, Otten UH. Interleukin-6 (IL-6) - a molecule with both beneficial and destructive potentials. Prog. Neurobiol. 52(5), 379-390 (1997).
62. Gruol DL, Nelson TE. Physiological and pathological roles of interleukin-6 in the central nervous system. Mol. Neurobiol. 15(3), 307-339 (1997).
63. Nakashima K, Wiese S, Yanagisawa M et al. Developmental requirement of gp130 signaling in neuronal survival and astrocyte differentiation. J. Neurosci. 19(13), 5429-5434 (1999).
64. Strauss S, Bauer J, Ganter U, Jonas U, Berger M, Volk B. Detection of interleukin-6 and α-2-macroglobulin immunoreactivity in cortex and hippocampus of Alzheimer's disease patients. Lab. Invest. 66, 223-230 (1992).
65. Huell M, Strauss S, Volk B, Berger M, Bauer J. Interleukin-6 present in early stage of plaque formation and is restricted to the brain of Alzheimer's disease patients. Acta Neuropathol. 89, 544-551 (1995).
66. Fishman D, Faulds G, Jeffery R et al. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J. Clin. Invest. 102(7), 1369-1376 (1998).
67. Licastro F, Grimaldi LM, Bonafe M et al. Interleukin-6 gene alleles affect the risk of Alzheimer's disease and levels of the cytokine in blood and brain. Neurobiol. Aging 24(7), 921-926 (2003).
68. Bagli M, Papassotiropoulos A, Knapp M et al. Association between an interleukin-6 promoter and 3′ flanking region haplotype and reduced Alzheimer's disease risk in a German population. Neurosci. Lett. 283(2), 109-112 (2000).
69. Papassotiropoulos A, Bagli M, Jessen F et al. A genetic variation of the inflammatory cytokine interleukin-6 delays the initial onset and reduces the risk for sporadic Alzheimer's disease. Ann. Neurol. 45(5), 666-668 (1999). • First paper describing a genetic link of an IL-6 variable number tandem repeat (VNTR) polymorphism with a reduced risk of AD.
70. Pola R, Flex A, Gaetani E et al. The -174 G/C polymorphism of the interleukin-6 gene promoter is associated with Alzheimer's disease in an Italian population [corrected]. Neuroreport 13(13), 1645-1647 (2002).
71. Faltraco F, Burger K, Zill P et al. Interleukin-6-174 G/C promoter gene polymorphism C allele reduces Alzheimer's disease risk. J. Am. Geriatr. Soc. 51(4), 578-579 (2003).
72. Depboylu C, Lohmuller F, Gocke P et al. An interleukin-6 promoter variant is not associated with an increased risk for Alzheimer's disease. Dement. Geriatr. Cogn. Disord. 17(3), 170-173 (2004).
73. Bhojak TJ, DeKosky ST, Ganguli M, Kamboh MI. Genetic polymorphisms in the cathespin D and interleukin-6 genes and the risk of Alzheimer's disease. Neurosci. Lett. 288(1), 21-24 (2000).
74. Licastro F, Porcellini E, Caruso C, Lio D, Corder EH. Genetic risk profiles foe Alzheimer's disease: integration of APOE genotype and gene variants that up-regulate inflammation. Neurobiol. Aging (2006) (In press).
75. Moore KW, de Waal MR, Coffman RL, O'Garra A. Interleukin-10 and the interleukin-10 receptor. Annu. Rev. Immunol. 19, 683-765 (2001).
76. Sato K, Nagayama H, Tadokoro K, Juji T, Takahashi TA. Extracellular signal-regulated kinase, stress-activated protein kinase/c-Jun N-terminal kinase, and p38mapk are involved in IL-10-mediated selective repression of TNF-alpha-induced activation and maturation of human peripheral blood monocyte-derived dendritic cells. J. Immunol. 162(7), 3865-3872 (1999).
77. Mizuno T, Sawada M, Marunouchi T, Suzumura A. Production of interleukin-10 by mouse glial cells in culture. Biochem. Biophys. Res. Commun. 205(3), 1907-1915 (1994).
78. Strle K, Zhou JH, Shen WH et al. Interleukin-10 in the brain. Crit. Rev. Immunol. 21(5), 427-449 (2001).
79. Gibson AW, Edberg JC, Wu J, Westendorp RG, Huizinga TW, Kimberly RP. Novel single nucleotide polymorphisms in the distal IL-10 promoter affect IL-10 production and enhance the risk of systemic lupus erythematosus. J. Immunol. 166(6), 3915-3922 (2001).
80. Tagore A, Gonsalkorale WM, Pravica V et al. Interleukin-10 (IL-10) genotypes in inflammatory bowel disease. Tissue Antigens 54(4), 386-390 (1999).
81. Lio D, Licastro F, Scola L et al. Interleukin-10 promoter polymorphism in sporadic Alzheimer's disease. Genes Immun. 4(3), 234-238 (2003). • Interesting paper describing a genetic link of an IL-10 aplotype with increased AD risk.
82. Depboylu C, Du Y, Muller U et al. Lack of association of interleukin-10 promoter region polymorphisms with Alzheimer's disease. Neurosci. Lett. 342(1-2), 132-134 (2003).
83. Arosio B, Trabattoni D, Galimberti L et al. Interleukin-10 and interleukin-6 gene polymorphisms as risk factors for Alzheimer's disease. Neurobiol. Aging 25(8), 1009-1015 (2004)
84. Scassellati C, Zanardini R, Squitti R et al. Promoter haplotypes of interleukin-10 gene and sporadic Alzheimer's disease. Neurosci. Lett. 356(2), 119-122 (2004).
85. Travis J, Salvelsen GS. Human plasma proteinase inhibitors. Annu. Rev. Biochem. 52, 655-709 (1983).
86. Furby A, Leys D, Delacourte A, Buee L, Soetaert G, Petit H. Are α-1-antichymotrypsin and inter-α-trypsin inhibitor peripheral markers of Alzheimer's disease? J. Neurol. Neurosurg. Psychiatry 54(5), 469 (1991).
87. Eriksson S, Janciauskiene S, Lannfelt L. Alpha 1-antichymotrypsin regulates Alzheimer beta-amyloid peptide fibril formation. Proc. Natl Acad. Sci. USA 92(6), 2313-2317 (1995).
88. Licastro F, Morini MC, Polazzi E, Davis LJ. Increased serum a-1-antichymotrypsin in patients with probable Alzheimer's disease: an acute-phase reactant without the peripheral acute-phase response. J. Neuroimmunol. 57, 71-75 (1995).
89. Licastro F, Parnetti L, Morini MC et al. acute-phase reactant α-1-antichymotrypsin is increased in cerebrospinal fluid and serum of patients with probable Alzheimer's disease. Alzheimer Dis. Assoc. Disord. 9, 112-118 (1995).
90. Kamboh MI, Sanghera DK, Ferrel RE, DeKosky ST. APOE 4 associated Alzheimer's disease risk is modified by α-1-antichymotrypsin polymorphism. Nat. Genet. 10, 486-488 (1995). • First paper describing an association of an antichymotripsin (ACT) signal peptide polymorphism with increased AD risk.
91. Haines JL, Prochard ML, Saunders AM et al. No genetic effect of α-1-antichymotrypsin in Alzheimer's disease. Genomics 33, 53-56 (1996).
92. Licastro F, Pedrini S, Govoni M et al. Apolipoprotein E and α-1-antichymotrypsin allele polymorphism in sporadic and familiar Alzheimer's disease. Neurosci. Lett. 270, 129-132 (1999).
93. Kamboh MI, Minster RL, Kenney M et al. α-1-antichymotrypsin (ACT or SERPINA3) polymorphism may affect age-at-onset and disease duration of Alzheimer's disease. Neurobiol. Aging 27(10) 1435-1439 (2005).
94. Licastro F, Pedrini S, Ferri C et al. Gene polymorphism affecting α-1-antichymotrypsin and interleukin-1 plasma levels increases Alzheimer's disease risk. Ann. Neurol. 48, 388-391 (2000).
95. Morgan K, Licastro F, Tilley L, Ritchie A, Pedrini S, Kalsheker N. Polymorphism in the α-1-antichymotrypsin (ACT) gene promoter: effect on expression in transfected glial and liver cells lines and plasma ACT concentrations. Hum. Genet. 109, 303-310 (2001).
96. Licastro F, Chiappelli M, Grimaldi LM et al. A new promoter polymorphism in the alpha-1-antichymotrypsin gene is a disease modifier of Alzheimer's disease. Neurobiol. Aging 26(4), 449-53 (2005). • First paper describing an association of ACT polymorphism in the promoter region with increased AD risk and accelerated cognitive deterioration.
97. Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature 343, 425-430 (2000).
98. Zhang FL, Casey PJ. Protein prenylation: molecular mechanisms and functional consequences. Annu. Rev. Biochem. 65, 241-269 (1996).
99. Chong PH, Kezele R, Franklin C. High-density lipoprotein cholesterol and the role of statins. Circ. J. 66, 1037-1044 (2002).
100. Rockwood K, Kirkland S, Hogan DB et al. Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people. Arch. Neurol. 59, 223-227 (2002).
101. Kuodinov AR, Berezov TT, Kuodinova NV. Alzheimer's amyloid beta and lipid metabolism: a missing link? FASEB 12, 1097-1099 (1998). • Important paper stressing a possible direct role of cholesterol metabolism alteration in AD.
102. Ignatius MJ, Shooter EM, Pitas RE, Mahley RW. Lipoprotein uptake by neuronal growth cones in vitro. Science 236, 959-962 (1987).
103. Frears ER, Stephens DJ, Walters CE, Davies H, Austen BM. The role of cholesterol in the biosynthesis of β-amyloid. Neuroreport 10, 1699-1705 (1999).
104. Grimm MO, Grimm HS, Patzold AJ et al. Regulation of cholesterol and sphingomyelin metabolism by amyloid-β and presenilin. Nat. Cell. Biol. 7(11), 1118-1123 (2005).
105. Sorrentino S, Landmesser U. Nonlipid-lowering effects of statins. Curr. Treat. Options Cardiovasc. Med. 7(6), 459-566 (2005).
106. Cordle A, Landreth G. 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors attenuate β-amyloid-induced microglial inflammatory responses. J. Neurosci. 25(2), 299-307 (2005).
107. Stuve O, Youssef S, Steinman L, Zamvil SS. Statins as potential therapeutic agents in neuroinflammatory disorders. Curr. Opin. Neurol. 16(3), 393-401 (2003).
108. Walsh S, Aisen P. Inflammatory processes and Alzheimer's disease. Expert Rev. Neurotherapeutics 4(5), 793-798 (2004).