Angiotensin-converting enzyme as a potential target for treatment of Alzheimer's disease: Inhibition or activation?

Reviews in the Neurosciences

Volumn 19, Issue 4-5, 2008, Pages 203-212

  Zou, Kun ^a   Michikawa, Makoto ^b  

^a IWATE MEDICAL UNIVERSITY   (Japan)

^b NATIONAL CENTER FOR GERIATRICS AND GERONTOLOGY   (Japan)

Author keywords

angiotensin converting enzyme (ACE), Alzheimer's

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN[1-40]; AMYLOID BETA PROTEIN[1-42]; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CALCIUM CHANNEL BLOCKING AGENT; DIPEPTIDYL CARBOXYPEPTIDASE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DIURETIC AGENT; PERINDOPRIL;

ALZHEIMER DISEASE; CLINICAL TRIAL; DRUG TARGETING; ENZYME ACTIVATION; ENZYME INHIBITION; ENZYME POLYMORPHISM; GENETIC ANALYSIS; HUMAN; HYPERTENSION; MILD COGNITIVE IMPAIRMENT; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; REVIEW;

EID: 57349100336     PISSN: 03341763     EISSN: None     Source Type: Journal    
DOI: 10.1515/REVNEURO.2008.19.4-5.203     Document Type: Review

References (95)

1. Alhenc-Gelas F, Richard J, Courbon D, Warnet JM, Corvol P. Distribution of plasma angiotensin I-converting enzyme levels in healthy men: relationship to environmental and hormonal parameters. J Lab Clin Med 1991;117:33-39.
2. Alvarez R, Alvarez V, Lahoz CH, Martinez C, Pena J, Sanchez JM, Guisasola LM, Salas-Puig J, Moris G, Vidal JA, Ribacoba R, Menes BB, Uria D, Coto E. Angiotensin converting enzyme and endothelial nitric oxide synthase DNA polymorphisms and late onset Alzheimer's disease. J Neurol Neurosurg Psychiatry 1999;67:733-736.
3. Amouyel P, Richard F, Cottel D, Amant C, Codron V, Helbecque N. The deletion allele of the angiotensin I converting enzyme gene as a genetic susceptibility factor for cognitive impairment. Neurosci Lett 1996;217:203-205.
4. Barnes JM, Barnes NM, Costall B, Coughlan J, Kelly ME, Naylor RJ, Tomkins DM, Williams TJ. Angiotensin-converting enzyme inhibition, angiotensin, and cognition. J Cardiovasc Pharmacol 1992;19 (Suppl 6): S63-71.
5. Bartres-Faz D, Junque C, Clemente IC, Lopez-Alomar A, Valveny N, Lopez-Guillen A, Lopez T, Cubells MJ, Moral P. Angiotensin I converting enzyme polymorphism in humans with age-associated memory impairment: relationship with cognitive performance. Neurosci Lett 2000;290:177-180.
6. Bentahir M, Nyabi O, Verhamme J, Tolia A, Horre K, Wiltfang J, Esselmann H, De Strooper B. Presenilin clinical mutations can affect gamma-secretase activity by different mechanisms. J Neurochem 2006;96:732-742.
7. Binevski PV, Sizova EA, Pozdnev VF, Kost OA. Evidence for the negative cooperativity of the two active sites within bovine somatic angiotensin- converting enzyme. FEBS Lett 2003;550:84-88.
8. Birkenhager WH, Forette F, Staessen JA. Dementia and antihypertensive treatment. Curr Opin Nephrol Hypertens 2004;13:225-230.
9. Borchelt DR, Thinakaran G, Eckman CB, Lee MK, Davenport F, Ratovitsky T, Prada CM, Kim G, Seekins S, Yager D, Slunt HH, Wang R, Seeger M, Levey AI, Gandy SE, Copeland NG, Jenkins NA, Price DL, Younkin SG, Sisodia SS. Familial Alzheimer's diseaselinked presenilin 1 variants elevate Aβ1-42/1-40 ratio in vitro and in vivo. Neuron 1996;17:1005-1013.
10. Cambien F, Poirier O, Lecerf L, Evans A, Cambou JP, Arveiler D, Luc G, Bard JM, Bara L, Ricard S, et al. Deletion polymorphism in the gene for angiotensinconverting enzyme is a potent risk factor for myocardial infarction. Nature 1992;359:641-644.
11. Chapman J, Wang N, Treves TA, Korczyn AD, Bornstein NM. ACE, MTHFR, factor V Leiden, and APOE polymorphisms in patients with vascular and Alzheimer's dementia. Stroke 1998;29:1401-1404.
12. Chiu AT, Herblin WF, McCall DE, Ardecky RJ, Carini DJ, Duncia JV, Pease LJ, Wong PC, Wexler RR, Johnson AL, et al. Identification of angiotensin II receptor subtypes. Biochem Biophys Res Commun 1989;165:196-203.
13. Costerousse O, Allegrini J, Lopez M, Alhenc-Gelas F. Angiotensin I-converting enzyme in human circulating mononuclear cells: genetic polymorphism of expression in T-lymphocytes. Biochem J 1993;290:33-40.
14. Cuajungco MP, Goldstein LE, Nunomura A, Smith MA, Lim JT, Atwood CS, Huang X, Farrag YW, Perry G, Bush AI. Evidence that the beta-amyloid plaques of Alzheimer's disease represent the redox-silencing and entombment of Aβ by zinc. J Biol Chem 2000;275:19439-19442.
15. Cummings BJ, Pike CJ, Shankle R, Cotmaii CW. Betaamyloid deposition and other measures of neuropathology predict cognitive status in Alzheimer's disease. Neurobiol Aging 1996;17:921-933.
16. Danser AH, Schalekamp MA, Bax WA, van den Brink AM, Saxena PR, Riegger GA, Schunkert H. Angiotensin-converting enzyme in the human heart. Effect of the deletion/insertion polymorphism. Circulation 1995;92:1387-1388.
17. Eckman EA, Adams SK, Troendle FJ, Stodola BA, Kahn MA, Fauq AH, Xiao HD, Bernstein KE, Eckman CB. Regulation of steady-state beta-amyloid levels in the brain by neprilysin and endothelin-converting Enzyme but not angiotensin-converting enzyme. J Biol Chem 2006;281:30471-30478.
18. Elkins JS, Douglas VC, Johnston SC. Alzheimer disease risk and genetic variation in ACE: a meta-analysis. Neurology 2004;62:363-368.
19. Enseleit F, Hurlimann D, Luscher TF. Vascular protective effects of angiotensin converting enzyme inhibitors and their relation to clinical events. J Cardiovasc Pharmacol 2001;37 (Suppl 1): S21-30.
20. Farrer LA, Sherbatich T, Keryanov SA, Korovaitseva GI, Rogaeva EA, Petruk S, Premkumar S, Moliaka Y, Song YQ, Pei Y, Sato C, Selezneva ND, Voskresenskaya S, Golimbet V, Sorbi S, Duara R, Gavrilova S, St George-Hyslop PH, Rogaev El. Association between angiotensin-converting enzyme and Alzheimer disease. Arch Neurol 2000;57:210-214.
21. Forman MS, Mufson EJ, Leurgans S, Pratico D, Joyce S, Leight S, Lee VM, Trojanowski JQ. Cortical biochemistry in MCI and Alzheimer disease: lack of correlation with clinical diagnosis. Neurology 2007;68:757-763.
22. Galinsky D, Tysoe C, Brayne CE, Easton DF, Huppert FA, Dening TR, Paykel ES, Rubinsztein DC. Analysis of the apo E/apo C-I, angiotensin converting enzyme and methylenetetrahydrofolate reductase genes as candidates affecting human longevity. Atherosclerosis 1997;129:177-183.
23. Gard PR, Rusted JM. Angiotensin and Alzheimer's disease: therapeutic prospects. Expert Rev Neurother 2004;4:87-96.
24. Gerlai R. Alzheimer's disease: beta-amyloid hypothesis strengthened! Trends Neurosci 2001;24:199.
25. Giannakopoulos P, Herrmann FR, Bussiere T, Bouras C, Kovari E, Perl DP, Morrison JH, Gold G, Hof PR. Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease. Neurology 2003;60:1495-1500.
26. Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L, et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 1991;349:704-706.
27. Guillozet AL, Weintraub S, Mash DC, Mesulam MM. Neurofibrillary tangles, amyloid, and memory in aging and mild cognitive impairment. Arch Neurol 2003;60:729-736.
28. Hemming ML, Selkoe DJ. Amyloid beta-protein is degraded by cellular angiotensin-converting enzyme (ACE) and elevated by an ACE inhibitor. J Biol Chem 2005;280:37644-37650.
29. Hemming ML, Selkoe DJ, Farris W. Effects of prolonged angiotensin-converting enzyme inhibitor treatment on amyloid beta-protein metabolism in mouse models of Alzheimer disease. Neurobiol Dis 2007;26:273-281.
30. Hu J, Igarashi A, Kamata M, Nakagawa H. Angiotensinconverting enzyme degrades Alzheimer amyloid betapeptide (A beta); retards A beta aggregation, deposition, fibril formation; and inhibits cytotoxicity. J Biol Chem 2001;276:47863-47868.
31. Hu J, Miyatake F, Aizu Y, Nakagawa H, Nakamura S, Tamaoka A, Takahash R, Urakami K, Shoji M. Angiotensin-converting enzyme genotype is associated with Alzheimer disease in the Japanese population. Neurosci Lett 1999;277:65-67.
32. Huang W, Gallois Y, Bouby N, Bruneval P, Heudes D, Belair MF, Krege JH, Meneton P, Marre M, Smithies O, Alhenc-Gelas F. Genetically increased angiotensin I- converting enzyme level and renal complications in the diabetic mouse. Proc Natl Acad Sci USA 2001;98:13330-13334.
33. Iwatsubo T, Odaka A, Suzuki N, Mizusawa H, Nukina N, Ihara Y. Visualization of A beta 42(43) and A beta 40 in senile plaques with end-specific A beta monoclonals: evidence that an initially deposited species is A beta 42(43). Neuron 1994;13:45-53.
34. Jeunemaitre X, Lifton RP, Hunt SC, Williams RR, Lalouel JM. Absence of linkage between the angiotensin converting enzyme locus and human essential hypertension. Nat Genet 1992;1:72-75.
35. Josephs KA, Whitwell JL, Ahmed Z, Shiung MM, Weigand SD, Knopman DS, Boeve BF, Parisi JE, Petersen RC, Dickson DW, Jack CR Jr. Beta-amyloid burden is'not associated with rates of brain atrophy. Ann Neurol 2008;63:204-212.
36. Kehoe PG, Katzov H, Feuk L, Bennet AM, Johansson B, Wiman B, de Faire U, Cairns NJ, Wilcock GK, Brookes AJ, Blennow K, Prince JA. Haplotypes extending across ACE are associated with Alzheimer's disease. Hum Mol Genet 2003;12:859-867.
37. Kehoe PG, Russ C, Mcllory S, Williams H, Holmans P, Holmes C, Liolitsa D, Vahidassr D, Powell J, McGleenon B, Liddell M, Plomin R, Dynan K, Williams N, Neal J, Cairns NJ, Wilcock G, Passmore P, Lovestone S, Williams J, Owen MJ. Variation in DCP1, encoding ACE, is associated with susceptibility to Alzheimer disease. Nat Genet 1999;21:71-72.
38. Kehoe PG, Wilcock GK. Is inhibition of the renin-angiotensin system a new treatment option for Alzheimer's disease? Lancet Neurol 2007;6:373-378.
39. Khachaturian AS, Zandi PP, Lyketsos CG, Hayden KM, Skoog 1, Norton MC, Tschanz JT, Mayer LS, Welsh- Bohmer KA, Breitner JC. Antihypertensive medication use and incident Alzheimer disease: the Cache County Study. Arch Neurol 2006;63:686-692.
40. Kim J, Onstead L, Randle S, Price R, Smithson L, Zwizinski C, Dickson DW, Golde T, McGowan E. AP40 inhibits amyloid deposition in vivo. J Neurosci 2007;27:627-633.
41. Kontush A, Berndt C, Weber W, Akopyan V, Arlt S, Schippling S, Beisiegel U. Amyloid-beta is an antioxidant for lipoproteins in cerebrospinal fluid and plasma. Free Radic Biol Med 2001;30:119-128.
42. Krege JH, Kim HS, Moyer JS, Jennette JC, Peng L, Hiller SK, Smithies O. Angiotensin-converting enzyme gene mutations, blood pressures, and cardiovascular homeostasis. Hypertension 1997;29:150-157.
43. Lee HG, Zhu X, Castellani RJ, Nunomura A, Perry G, Smith MA. Amyloid-beta in Alzheimer disease: the null versus the alternate hypotheses. J Pharmacol Exp Ther 2007;321:823-829.
44. Lehmann DJ, Cortina-Borja M, Warden DR, Smith AD, Sleegers K, Prince JA, van Duijn CM, Kehoe PG. Large meta-analysis establishes the ACE insertion-deletion polymorphism as a marker of Alzheimer's disease. Am J Epidemiol 2005;162:305-317.
45. Lendon CL, Ashall F, Goate AM. Exploring the etiology of Alzheimer disease using molecular genetics. JAMA 1997;277:825-831.
46. Louis WJ, Mander AG, Dawson M, O'Callaghan C, Conway EL. Use of computerized neuropsychological tests (CANTAB) to assess cognitive effects of antihypertensive drugs in the elderly. Cambridge Neuropsychological Test Automated Battery. J Hypertens 1999;17:1813-1819.
47. Maeda Y, Ikeda U, Ebata H, Hojo Y, Seino Y, Hayashi Y, Kuroki S, Shimada K. Angiotensin-converting enzyme gene polymorphism in hypertensive individuals with parental history of stroke. Stroke 1996;27:1521-1523.
48. Mann DM, Jones D, South PW, Snowden JS, Neary D. Deposition of amyloid beta protein in non-Alzheimer dementias: evidence for a neuronal origin of parenchymal deposits of beta protein in neurodegenerative disease. Acta Neuropathol (Berl) 1992;83:415-419.
49. Manila KM, Rinne JO, Roytta M, Laippala P, Pietila T, Kalimo H, Koivula T, Frey H, Lehtimaki T. Dipeptidyl carboxypeptidase 1 (DCP1) and butyrylcholinesterase (BCHE) gene interactions with the apolipoprotein E e4 allele as risk factors in Alzheimer's disease and in Parkinson's disease with coexisting Alzheimer pathology. J Med Genet 2000;37:766-770.
50. McGowan E, Pickford F, Kim J, Onstead L, Eriksen J, Yu C, Skipper L, Murphy MP, Beard J, Das P, Jansen K, Delucia M, Lin WL, Dolios G, Wang R, Eckman CB, Dickson DW, Hutton M, Hardy J, Golde T. Aβ42 is essential for parenchymal and vascular amyloid deposition in mice. Neuron 2005;47:191-199.
51. Meng Y, Baldwin CT, Bowirrat A, Waraska K, Inzelberg R, Friedland RP, Farrer LA. Association of polymorphisms in the angiotensin-converting enzyme gene with Alzheimer disease in an Israeli Arab community. Am J Hum Genet 2006;78:871-877.
52. Monastero R, Caldarella R, Mannino M, Cefalu AB, Lopez G, Noto D, Camarda C, Camarda LK, Notarbartolo A, Avema MR, Camarda R. Lack of association between angiotensin converting enzyme polymorphism and sporadic Alzheimer's disease. Neurosci Lett 2002;335:147-149.
53. Montgomery HE, Marshall R, Hemingway H, Myerson S, Clarkson P, Dollery C, Hayward M, Holliman DE, Jubb M, World M, Thomas EL, Brynes AE, Saeed N, Barnard M, Bell JD, Prasad K, Rayson M, Talmud PJ, Humphries SE. Human gene for physical performance. Nature 1998;393:221-222.
54. ε4 on the initial phase of amyloid beta-protein accumulation in the human brain. Am J Pathol 2000;157:2093-2099.
55. Mucke L, Masliah E, Yu GQ, Mallory M, Rockenstein EM, Tatsuno G, Hu K, Kholodenko D, Johnson-Wood K, McConlogue L. High-level neuronal expression of Aβ 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci 2000;20:4050-4058.
56. Mueller-Steiner S, Zhou Y, Arai H, Roberson ED, Sun B, Chen J, Wang X, Yu G, Esposito L, Mucke L, Gan L. Antiamyloidogenic and neuroprotective functions of cathepsin B: implications for Alzheimer's disease. Neuron 2006;51:703-714.
57. Narain Y, Yip A, Murphy T, Brayne C, Easton D, Evans JG, Xuereb J, Cairns N, Esiri MM, Furlong RA, Rubinsztein DC. The ACE gene and Alzheimer's disease susceptibility. J Med Genet 2000;37:695-697.
58. Naslund J, Haroutunian V, Mohs R, Davis KL, Davies P, Greengard P, Buxbaum JD. Correlation between elevated levels of amyloid beta-peptide in the brain and cognitive decline. JAMA 2000;283:1571-1577.
59. Ng DP, Tai BC, Koh D, Tan KW, Chia KS. Angiotensin-I converting enzyme insertion/deletion polymorphism and its association with diabetic nephropathy: a meta-analysis of studies reported between 1994 and 2004 and comprising 14,727 subjects. Diabetologia 2005;48:1008-1016.
60. Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Balraj EK, Jones PK, Ghanbari H, Wataya T, Shimohama S, Chiba S, Atwood CS, Petersen RB, Smith MA. Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol 2001;60:759-767.
61. Nunomura A, Perry G, Pappolla MA, Friedland RP, Hirai K, Chiba S, Smith MA. Neuronal oxidative stress precedes amyloid-beta deposition in Down syndrome. J Neuropathol Exp Neurol 2000;59:1011-1017.
62. Oba R, Igarashi A, Kamata M, Nagata K, Takano S, Nakagawa H. The N-terminal active centre of human angiotensin-converting enzyme degrades Alzheimer amyloid beta-peptide. Eur J Neurosci 2005;21:733-740.
63. Ohrui T, Matsui T, Yamaya M, Arai H, Ebihara S, Maruyama M, Sasaki H. Angiotensin-converting enzyme inhibitors and incidence of Alzheimer's disease in Japan. J Am Geriatr Soc 2004;52:649-650.
64. Ohrui T, Tomita N, Sato-Nakagawa T, Matsui T, Maruyama M, Niwa K, Arai H, Sasaki H. Effects of brain-penetrating ACE inhibitors on Alzheimer disease progression. Neurology 2004;63:1324-1325.
65. Patterson D, Gardiner K, Kao FT, Tanzi R, Watkins P, Gusella JF. Mapping of the gene encoding the betaamyloid precursor protein and its relationship to the Down syndrome region of chromosome 21. Proc Natl Acad Sci USA 1988;85:8266-8270.
66. Plant LD, Boyle JP, Smith IF, Peers C, Pearson HA. The production of amyloid beta peptide is a critical requirement for the viability of central neurons. J Neurosci 2003;23:5531-5535.
67. Richard F, Berr C, Amant C, Helbecque N, Amouyel P, Alperovitch A. Effect of the angiotensin I-converting enzyme I/D polymorphism on cognitive decline. The EVA Study Group. Neurobiol Aging 2000;21:75-80.
68. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990;86:1343-1346.
69. Rosenkranz AC, Lob H, Breitenbach T, Berkels R, Roesen R. Endothelial antioxidant actions of dihydropyridines and angiotensin converting enzyme inhibitors. Eur J Pharmacol 2006;529:55-62.
70. Rozzini L, Chilovi BV, Bertoletti E, Conti M, Del Rio I, Trabucchi M, Padovani A. Angiotensin converting enzyme (ACE) inhibitors modulate the rate of progression of amnestic mild cognitive impairment. Int J Geriatr Psychiatry 2006;21:550-555.
71. Savaskan E. The role of the brain renin-angiotensin system in neurodegenerative disorders. Curr Alzheimer Res 2005;2:29-35.
72. Sayed-Tabatabaei FA, Houwing-Duistermaat JJ, van Duijn CM, Witteman JC. Angiotensin-converting enzyme gene polymorphism and carotid artery wall thickness: a meta-analysis. Stroke 2003;34:1634-1639.
73. Sayed-Tabatabaei FA, Oostra BA, Isaacs A, van Duijn CM, Witteman JC. ACE polymorphisms. Circ Res 2006;98:1123-1133.
74. Scacchi R, De Bernardini L, Mantuano E, Vilardo T, Donini LM, Ruggeri M, Gemma AT, Pascone R, Corbo RM. DNA polymorphisms of apolipoprotein B and angiotensin I-converting enzyme genes and relationships with lipid levels in Italian patients with vascular dementia or Alzheimer's disease. Dement Geriatr Cogn Disord 1998;9:186-190.
75. Schachter F, Faure-Delanef L, Guenot F, Rouger H, Froguel P, Lesueur-Ginot L, Cohen D. Genetic associations with human longevity at the APOE and ACE loci. Nat Genet 1994;6:29-32.
76. Scheuner D, Eckman C, Jensen M, Song X, Citron M, Suzuki N, Bird TD, Hardy J, Hutton M, Kukull W, Larson E, Levy-Lahad E, Viitanen M, Peskind E, Poorkaj P, Schellenberg G, Tanzi R, Wasco W, Lannfelt L, Selkoe D, Younkin S. Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin I and 2 and APP mutations linked to familial Alzheimer's disease. NatMed 1996;2:864-870.
77. Schmidt S, van Hooft IM, Grobbee DE, Ganten D, Ritz E. Polymorphism of the angiotensin I converting enzyme gene is apparently not related to high blood pressure: Dutch Hypertension and Offspring Study. J Hypertens 1993;11:345-348.
78. Schmitt FA, Davis DG, Wekstein DR, Smith CD, Ashford JW, Markesbery WR, "Preclinical" AD revisited: neuropathology of cognitively normal older adults. Neurology 2000:55: 370-376.
79. Selkoe DJ. Normal and abnormal biology of the betaamyloid precursor protein. Annu Rev Neurosci 1994;17:489-517.
80. Selkoe DJ. Alzheimer disease: mechanistic understanding predicts novel therapies. Ann Intern Med 2004;140:627-638.
81. Sharma P. Meta-analysis of the ACE gene in ischaemic stroke. J Neurol Neurosurg Psychiatry 1998;64:227-230.
82. Sibony M, Gasc JM, Soubrier F, Alhenc-Gelas F, Corvol P. Gene expression and tissue localization of the two isoforms of angiotensin I converting enzyme. Hypertension 1993;21:827-835.
83. Skeggs LT Jr, Kahn JR, Shumway NP. The preparation and function of the hypertensin-converting enzyme. J Exp Med 1956;103:295-299.
84. Sleegers K, den Heijer T, van Dijk EJ, Hofman A, Bertoli-Avella AM, Koudstaal PJ, Breteler MM, van Duijn CM. ACE gene is associated with Alzheimer's disease and atrophy of hippocampus and amygdala. Neurobiol Aging 2005;26:1153-1159.
85. Sudilovsky A, Cutler NR, Sramek JJ, Wardle T, Veroff AE, Mickelson W, Markowitz J, Repetti S. A pilot clinical trial of the angiotensin-converting enzyme inhibitor ceranapril in Alzheimer disease. Alzheimer Dis Assoc Disord 1993;7:105-111.
86. Turner AJ, Hooper NM. The angiotensin-converting enzyme gene family: genomics and pharmacology. Trends Pharmacol Sci 2002;23:177-183.
87. von Bohlen und Halbach O, Albrecht D. The CNS reninangiotensin system. Cell Tissue Res 2006;326:599-616.
88. Wang B, Jin F, Yang Z, Lu Z, Kan R, Li S, Zheng C, Wang L. The insertion polymorphism in angiotensinconverting enzyme gene associated with the APOE epsilon 4 allele increases the risk of late-onset Alzheimer disease. J Mol Neurosci 2006;30:267-271.
89. Whitebread S, Mele M, Kamber B, de Gasparo M. Preliminary biochemical characterization of two angiotensin 11 receptor subtypes. Biochem Biophys Res Commun 1989;163:284-291.
90. Wright JW, Harding JW. Important role for angiotensin HI and IV in the brain renin-angiotensin system. Brain Res Brain Res Rev 1997;25:96-124.
91. Yang JD, Feng G, Zhang J, Lin ZX, Shen T, Breen G, St Clair D, He L. Association between angiotensin-converting enzyme gene and late onset Alzheimer's disease in Han Chinese. Neurosci Lett 2000;295:41-44.
92. Zou K, Gong JS, Yanagisawa K, Michikawa M. A novel function of monomeric amyloid beta-protein serving as an antioxidant molecule against metal-induced oxidative damage. J Neurosci 2002;22:4833-4841.
93. Zou K, Kim D, Kakio A, Byun K, Gong JS, Kim J, Kim M, Sawamura N, Nishimoto S, Matsuzaki K, Lee B, Yanagisawa K, Michikawa M Amyloid beta-protein (AP)1-40 protects neurons from damage induced by Api-42 in culture and in rat brain. J Neurochem 2003;87:609-619.
94. 1-40, and its inhibition enhances brain Aβ deposition. J Neurosci 2007;27:8628-8635.
95. Zubenko GS, Volicer L, Direnfeld LK, Freeman M, Langlais PJ, Nixon RA. Cerebrospinal fluid levels of angiotensin-converting enzyme in Alzheimer's disease, Parkinson's disease and progressive supranuclear palsy. Brain Res 1985;328:215-221.