簡易檢索 / 詳目顯示

研究生: 王秀觀
Hsiu-Kuan Wang
論文名稱: 台灣人族群阿茲海默氏症及血管型失智症的生物標記評估
Estimation of biomarker candidates for Alzheimer’s disease and/or vascular dementia in Taiwanese population
指導教授: 李桂楨
Lee, Guey-Jen
學位類別: 博士
Doctor
系所名稱: 生命科學系
Department of Life Science
論文出版年: 2009
畢業學年度: 97
語文別: 英文
論文頁數: 106
中文關鍵詞: 阿茲海默症血管型失智症遺傳變異疾病相關性基因表現分析
英文關鍵詞: Alzheimer’s disease, vascular dementia, genetic variation, disease association, expression analysis
論文種類: 學術論文
相關次數: 點閱:201下載:7
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
  • 阿茲海默症與血管型失智症是最普遍的兩類失智症。目前有關阿茲海默症的疾病診斷生物標記分子研究中,已知的遺傳標記分子有脂蛋白E基因4對偶基因、類澱粉蛋白前驅蛋白基因突變、早老素1及早老素2基因突變等。腦部及腦脊髓液中tau蛋白與類澱粉蛋白含量則為已確認的阿茲海默症疾病診斷蛋白標記分子。本研究利用台灣阿茲海默症、血管型失智症與正常人族群基因分型技術,分析候選基因多型性變異與疾病的相關性。結果發現脂蛋白E基因4對偶基因是阿茲海默症、而非血管型失智症的風險因子;血管收縮素轉換酶基因DD基因型、D對偶基因和-240 T – Alu D單套型是阿茲海默症與血管型失智症的風險因子;此外,實驗結果顯示介白素1基因-889 CT基因型對於70歲以上的血管型失智症罹病感受方面具有潛在的保護功能;同時,熱休克A5基因-415 AA/-180 GG基因型、-415 A/-180 G對偶基因會減低罹患阿茲海默症的風險。基因表現分析結果亦顯示,具有-415 A/-180 G對偶基因的細胞在遭受內質網壓力之後,其熱休克A5蛋白被誘發產生的程度明顯增加。由於尋找阿茲海默症淋巴細胞的生物標記的可行性,本論文亦分析了8個阿茲海默症及4個年齡、性別配合之正常人的APP蛋白型式及氧化蛋白,但未找到明顯的蛋白標記。以上實驗結果顯示,上述與阿茲海默症及/或血管型失智症的罹病相關的基因,可作為協助疾病診斷的遺傳標記分子。

    Alzheimer’s disease (AD) and vascular dementia (VaD) are the most prevalent forms of dementia. To date, the allelic variants of apolipoprotein E (APOE), genetic mutations in the amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2) genes, the levels of tau proteins and amyloid beta-peptides in brain and cerebrospinal fluid (CSF) are the well-documented biomarkers for AD. In the study, AD patients, VaD patients and ethnic-matched nondemented controls were analyzed by means of genotype association method. APOE 4 allele acts as risk factors only for Taiwanese AD, not for VaD. Angiotensin I-converting enzyme (ACE) DD genotype, ACE D allele and ACE -240 T – Alu D haplotype are risk factors for both AD and VaD. Besides, the results suggest a potential protective role of IL-1 -889 CT genotype in VaD susceptibility among Taiwanese over 70 years. Also a decrease in risk of developing AD for HSPA5 -415 AA/-180 GG genotype and HSPA5-415 A/-180 G allele was found. Expression analysis revealed that induction of HSPA5 expression after ER stress was markedly increased in the cells with the -415 A/-180 G allele. Since finding biomarkers in lymphocytes for AD is feasible, lymphoblastoid cells from 8 AD patients and 4 age-gender matched controls were used to study different APP forms and oxidized proteins associated with AD. However, no apparent protein marker was identified. Thus, the data suggested that genes involved in the prevalence of AD and/or VaD and may act as the genetic biomarkers for dementia diagnosis.

    Index Index I 摘要 IV Abstract V List of tables and figures VI Introduction 1 Alzheimer’s disease and vascular dementia 1 AD/VaD diagnostic biomarkers 1 Apolipoprotein E 2 Angiotensin I-converting enzyme 3 Tissue kallikrein 1 4 Interleukin-1α and interleukin-1β 4 HSPA5 chaperone 5 Protein candidate markers for Alzheimer’s disease 7 Amyloid precursor protein forms ratio as biomarker for AD 7 Oxidation-sensitive protein as biomarker for AD 9 Specific Aims 12 Aim 1. To identify probable genetic factors for AD and VaD 12 Aim 2. To identify protein biomarkers from transformed lymphoblasts from AD patients and controls 12 Materials and methods 13 I. Case-control study to identify genetic risk markers for dementia 13 Subjects 13 Genomic DNA extraction 14 Polymerase chain reaction (PCR) and genotyping 14 Statistical analysis 15 II. ACE promoter -240 A/T and Alu I/D reporter functional assay 16 Promoter constructs 16 (A) ACE-firefly/TK-Renilla dual luciferase reporter constructs 16 (B) ACE-firefly luciferase - Alu I/D reporter constructs (pGL3-ACE-A/T-I/D) 17 Preparation of electro-competent cells 17 Ligation 18 Electroporation 18 Minipreparation of plasmid DNA 18 Midipreparation of plasmid DNA 19 Cell cultivation 20 Promoter functional assay and statistical analysis 20 III. HSPA5 promoter SNPs and ER stress functional assay 21 Lymphoblastoid cell cultivation 21 RNA isolation 21 Real-time quantitative RT-PCR analysis of HSPA5 expression 22 IV. Western blot analysis of APP forms ratio 22 Cell lysate preparation 22 Western blotting and statistical analysis 23 V. Western blot analysis of oxidation-sensitive protein 24 Preparation of DNPH-derivatized proteins 24 Carbonyl immunreactivity assay and statistical analysis 24 Results 26 I. Case-control study to identify genetic risk markers for dementia 26 APOE, ACE and KLK1 gene polymorphisms and the risk of dementia 26 IL-1α and IL-1β gene promoter polymorphism and the risk of dementia 27 HSPA5 gene promoter polymorphism and the risk of dementia 28 II. ACE promoter functional study 30 ACE-firefly/TK-Renilla dual luciferase reporter constructs and assay 30 ACE-firefly luciferase - Alu I/D reporter constructs and assay 30 III. ER stress and HSPA5 expression study 31 IV. APP forms ratio study 31 V. Oxidation-modified protein study 32 Discussion 33 APOE, ACE and KLK1 gene polymorphisms and the risk of dementia 33 IL-1α and IL-1β gene promoter polymorphisms and the risk of dementia 36 HSPA5gene promoter polymorphism and the risk of dementia 38 APP forms ratio study 40 Oxidation-modified protein study 42 Conclusions 45 References 46 Legends for tables and figures 72

    劉國保 (2003) RAS系統和TGF-1的基因多型性與原發性VUR疾病發生和腎病進行的相關性研究。國立台灣師範大學生命科學系九十一學年度碩士論文。
    侯懿婷 (2005) 退化性神經疾病:PPP2R2B基因族群遺傳分析及分生研究。國立台灣師範大學生命科學系九十三學年度碩士論文。
    Abdi F, Quinn JF, Jankovic J, McIntosh M, Leverenz JB, Peskind E, Nixon R, Nutt J, Chung K, Zabetian C, Sammi A, Lin M, Hattan S, Pan C, Wang Y, Jin J, Zho D, Li GJ, Liu Y, Waichunas D, Montine TJ, Zhang J: Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders. J Alzheimer’s Dis 2006; 9: 293-348.
    Abecasis GR, Cookson WO: GOLD-graphical overview of linkage disequilibrium. Bioinformatics 2000; 16: 182-183.
    Adelman R, Saul RL, Ames BN: Oxidative damage to DNA: relation to species metabolic rate and life span. Proc Natl Acad Sci USA 1988; 85: 2706-2708.
    Akiyama H: Thrombin deposition in brains of patients with Alzheimer’s disease - activation of the coagulation system in the central nervous system. Rinsho Byori 1997; 104: 117-123.
    Aksenov MY, Akesenova MV, Butterfield DA, Geddes JW, Markesbery WR: Protein oxidation in the brain in Alzheimer’s disease. Neurosci 2001; 103: 373-383.
    Amici A, Levine RL, Tsai L, Stadtman ER: Conversion of amino acid residues in proteins and amino acid homopolymers to carbonyl derivatives by metal-catalyzed oxidation reactions. J Biol Chem 1989; 264: 3341-3346.
    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.
    Bailly S, di Giovine FS, Blakemore AI, Duff GW: Genetic polymorphism of human interleukin-1 alpha. Eur J Immunol 1993; 23: 1240-1245.
    Bang OY, Kwak YT, Joo IS, Huh K: Important link between dementia subtype and apolipoprotein E: a meta-analysis. Yonsei Med J 2003; 44: 401-413.
    Barley J, Blockwood A, Carter ND: Angiotensin converting enzyme insertion/deletion polymorphism. Association with ethnic origin. J Hypertens 1994; 12: 955-957.
    Baskin F, Rosenberg RN, Iyer L, Hynan L, Cullum CM: Platelet APP isoform ratios correlate with declining cognition in AD. Neurology 2000; 54: 1907-1909.
    Basu SK, Ho YK, Brown MS, Bilheimer DW, Anderson RGW, Goldstein JL: Biochemical and genetic studies of the apolipoprotein E secreted by mouse macrophages and human monocytes. J Biol Chem 1982; 257: 9788-9795.
    Beck KA, Nelson J: The spectrin-based membrane skeleton as a membrane protein-sorting machine. Am J Physiol 1996; 270: C1263-C1270.
    Beckman KB, Ames BN: Oxidative decay of DNA. J Biol Chem 1997; 272: 19633-19636.
    Berlett BS, Stadtman ER: Protein oxidation in aging, disease, and oxidative stress. J Biol Chem 1997; 272: 20313-20316.
    Beyreuther K, Masters CL: Amyloid precursor protein (APP) and A4 amyloid in the etiology of Alzheimer’s disease: Precursor-product relationships in the derangement of neuronal function. Brain Pathol 1991; 1: 241-251.
    Bhoola KD, Figueroa CD, Worthy K: Bioregulation of kinins: kallikreins, kininogens, and kininases. Pharmacol Rev 1992; 44: 1-80.
    Bickel H, Cooper B: Incidence and relative risk of dementia in an urban elderly population: findings of a prospective field study. Psychol Med 1994; 24: 179-192.
    Blennow K, Hampel H: CSF markers for incipient Alzheimer’s disease. Lancet Neurol 2003; 2: 605-613.
    Blum-Degen D, Muller T, Kuhn W, Geflach M, Przuntek H, Riederer P: Interleukin-1 and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer’s and de novo Parkinson’s disease patients. Neurosci Lett 1995; 202: 17-20.
    Borroni B, Colciaghi F, Pastorino L, Pettenati C, Cottini E, Rozzini L, Monastero R, Lenzi GL, Cattabeni F, Luca MD, Padovani A: Amyloid precursor protein in platelets of patients with Alzheimer’s disease: effect of acetylcholinesterase inhibitor treatment. Arch Neurol 2001; 58: 442-446.
    Borovecki F, Lovrecic L, Zhou J, Jeong H, Then F, Rosas HD, Hersch SM, Hogarth P, Bouzou B, Jensen RV, Krainc D: Genome-wide expression profiling of human blood reveals biomarkers for Huntington’s disease. Proc Natl Acad Sci USA 2005; 102: 11023-11028.
    Boyd-Kimball D, Castegna A, Sultana R, Poon HF, Petroze R, Lynn BC, Klein JB, Butterfield DA: Proteomic identification of proteins oxidized by A(1-42) in synaptosomes: implications for Alzheimer’s disease. Brain Res 2005; 1044: 206-215.
    Bush AI, Martins RN, Rumble B, Moir R, Fuller S, Milward E, Currie J, Ames D, Weidemann A, Fischer P, Multhaup G, Beyreuther K, Masters CL: The amyloid precursor protein of Alzheimer’s disease is released by human platelets. J Biol Chem 1990; 265: 15977-15983.
    Cacabelos R: Genomic characterization of Alzheimer’s disease and genotype-related phenotypic analysis of biological markers in dementia. Pharmacogenomics 2004; 5: 1049-1105.
    Cambien F, Poirier O, Lecerf L, Evans A, Cambou JP, Arveiler D, Luc G, Bard JM, Bara L, Ricard S, Tiret L, Amouyel P, Alhenc-Gelas F, Soubrier F: Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 1992; 359: 641-644.
    Cance B, Sies H, Boveris A: Hydroperoxide metabolism in mammalian organs. Physiol Rev 1979; 59: 527-605.
    Castegna A, Aksenov M, Aksenova M, Thongboonkerd V, Klein JB, Pierce WM, Booze R, Markesbery WR, Butterfield DA: Proteomic identification of oxidatively modified proteins in Alzheimer’s disease brain. Part I: creatine kinase BB, glutamine synthase, and ubiquitine carboxy-terminal hydrolase L-1. Free Radic Biol Med 2002; 33: 562-571.
    Catto A, Carter AM, Barrett JH, Stickland M, Bamford J, Davies JA, Grant PJ: Angiotensin-converting enzyme insertion/deletion polymorphism and cerebrovascular disease. Stroke 1996; 27: 435-440.
    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.
    Cheng CY, Hong CJ, Liu HC, Liu TY, Tsai SJ: Study of the association between Alzheimer’s disease and angiotensin-converting enzyme gene polymorphism using DNA from lymphocytes. Eur Neurol 2002; 47: 26-29.
    Cheverud JM: A simple correction for multiple comparisons in interval mapping genome scans. Heredity 2001; 87: 52-58.
    Choi J, Malakowsky CA, Talent JM, Conrad CC, Gracy RW: Idetification of oxidized plasma proteins in Alzheimer’s disease. Biochem Biophys Res Commun 2002; 293: 1566-1570.
    Choi J, Sullards MC, Olzmann JA, Rees HD, Weintraub ST, Bostwick DE, Gearing M, Levey AI, Chin L-S, Li L: Oxidative damage of DJ-1 is linked to sporadic Parkinson and Alzheimer diseases. J Biol Chem 2006; 281(16): 10816-10824.
    Colin E, Regulier E, Perrin V, Durr A, Brice A, Aebischer P, Deglon N, Humbert S, Saudou F: Akt is altered in an animal model of Huntington’s disease and in patients. Eur J Neurosci 2005; 21: 1478-1488.
    Conrad CC, Marshall PL, Talent JM, Malakowsky CA, Choi J, Gracy RW: Oxidized proteins in Alzheimer’s plasma. Biochem Biophys Res Commun 2000; 275: 678-681.
    Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA: Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 1993; 261: 921-923.
    Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R: Protein carbonyl groups as biomarkers of oxidative stress. Clin Clim Acta 2003; 329: 23-38.
    Davies KJA: Protein damage and degradation by oxygen radicals. I. General aspects. J Biol Chem 1987a; 262: 9895-9901.
    Davies KJA: Protein damage and degradation by oxygen radicals. II. Modification of amino acids. J Biol Chem 1987b; 262: 9902-9907.
    Davies TA, Long HJ, Sgro K, Rathbun WH, Mcmenamin ME, Seetoo K, Tibbles H, Billingslea AM, Fine RE, Fishman JB, Levesque CA, Smith SJ, Wells JM, Simons ER: Activated Alzheimer disease platelets retain more beta amyloid precursor protein. Neurobiology of Aging 1997; 18-2: 147-153.
    De La Torre JC: Vascular basis of Alzheimer’s pathogenesis. Ann N Y Acad Sci 2002; 977: 196-215.
    Dinarello CA, Wolff SM: The role of interleukin-1 in disease. N Engl J Med 1993; 328: 106-113.
    Dominici R, Cattaneo M, Malferrari G, Archi D, Mariani C, Grimaldi LM, Biunno I: Cloning and functional analysis of the allelic polymorphism in the transcription regulatory region of interleukin-1. Immunogenetics 2002; 54: 82-86.
    Du Y, Dodel RC, Eastwood BJ, Bales KR, Gao F, Lohmuller F, Muller U, Kurz A, Zimmer R, Evans RM, Hake A, Gasser T, Oertel WH, Griffin WS, Paul SM, Farlow MR: Association of an interleukin 1 polymorphism with Alzheimer’s disease. Neurology 2000; 55: 480-483.
    Duara R, BarkerWW, Lopez-Alberola R, Loewenstein DA, Grau LB, Gilchrist D, Sevush S, St George-Hyslop S: Alzheimer’s disease: interaction of apolipoprotein E genotype, family history of dementia, gender, education, ethnicity, and age of onset. Neurology 1996; 46: 1575–1579.
    Ehl C, Kolsch H, Ptok U, Jessen F, Schmitz S, Frahnert C, Schlosser R, Rao ML, Maier W, Heun R: Association of an interleukin-1beta gene polymorphism at position -899 with Alzheimer’s disease. Int J Mol Med 2003; 11: 235-238.
    Elkins JS, Douglas VC, Johnston SC: Alzheimer disease risk and genetic variation in ACE: a metaanalysis. Neurology 2004; 62: 363-368.
    Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, Myers RH, Pericak-Vance MA, Risch N, van Duijn CM: Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA 1997; 278: 1349-1356.
    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, George-Hyslop PH, Rogaev EI: Association between angiotensin-converting enzyme and Alzheimer disease. Arch Neurol 2000; 57: 210-214.
    Fidani L, Goulas A, Mirtsou V, Petersen RC, Tangalos E, Crook R, Hardy J: Interleukin- 1A polymorphism is not associated with late onset Alzheimer’s disease. Neurosci Lett 2002; 323: 81-83.
    Floyd RA: Antioxidants, oxidative stress, and degenerative neurological disorders. Proc Soc Exp Biol Med 1999; 222: 236-245.
    Gardella JE, Gorgone GA, Newman P, Frangione B, Gorevic PD: Characterization of Alzheimer amyloid precursor protein transcripts in platelets and megakaryocytes. Neurosci Lett 1992; 138: 229-232.
    Ghilardi JR, Catton M, Stimson ER, Rogers S, Walker LC, Maggio JE, Mantyh PW: Intra-arterial infusion of [I-125]A-1-40 labels amyloid deposits in the aged primate brain in vivo. Neuroreport 1996; 7: 2607-2612.
    Giulian D, Lachman LB: Interleukin-1 stimulation of astroglial proliferation after brain injury. Science 1985; 228: 497-499.
    Goate A. Chartier-Harlin M-C, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Mant R, Newton P, Rooke K, Roques P, Talbot C, Pericak-Vance M, Roses A, Williamson R, Rossor M, Owen M, Hardy J: Segregation of a missense mutation in amyloid precursor protein gene with familiar Alzheimer’s disease. Nature 1991; 349: 704-706.
    Goldgaber D, Harris HW, Hla T, Maciag T, Donnelly RJ, Jacobsen JS, Vitek MP, Gajdusek DC: Interleukin 1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells. Proc Natl Acad Sci USA 1989; 86: 7606-7610.
    Granger DN: Role of xanthine oxidase and granulocytes in ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 1988; 255: H1269-H1275.
    Grimaldi LM, Casadei VM, Ferri C, Veglia F, Licastro F, Annoni G, Biunno I, De Bellis G, Sorbi S, Mariani C, Canal N, Griffin WS, Franceschi M: Association of early-onset Alzheimer’s disease with an interleukin-1gene polymorphism. Ann Neurol 2000; 47: 361-365.
    Grundke-Iqbal I, Rolkova G, Konstekova E, Iqbal K: Biological markers in Alzheimer’s disease. Bratisl Lek Listy 2006; 107(9-10): 359-365.
    Hall SK, Perregaux DG, Gabel CA, Woodworth T, Durham LK, Huizinga TW, Breedveld FC, Seymour AB: Correlation of polymorphic variation in the promoter region of the interleukin-1gene with secretion of interleukin-1protein. Arthritis Rheum 2004; 50: 1976-1983.
    Halliwell B, Gutteridge JMC: Role of free radicals and catalytic metal ions in human diseases: an overiew. Methods in Enzymol 1990; 186: 1-85.
    Hampel H, Mitchell A, Blennow K, Frank RA, Brettschneider S, Weller L, et al.: Core biological marker candidates of Alzheimer’s disease-perspectives for diagnosis, prediction of outcome and reflection of biological activity. J Neural Transm 2004; 111: 247-272.
    Hardy J: Amyloid, the presenilins and Alzheimer’s disease. Trends Neurosci 1997; 20: 154-159.
    Harman D: The aging process. Proc Natl Acad Sci USA 1981; 78: 7124-7128.
    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 2002; 51: 795-797.
    Heinecke JW, Li W, Daehnke HL, Goldstein JA: Dityrosine, a specific marker of oxidation, is synthesized by the myeloperoxidase-hydrogen peroxidase system of human neutrophil and macrophages. J Biol Chem 1993; 268: 4069-4077.
    Hill WG: Estimation of linkage disequilibrium in randomly mating populations. Heredity 1974; 33: 229-239.
    Hoozemans JJ, Veerhuis R, Van Haastert ES, Rozemuller JM, Baas F, Eikelenboom P, Scheper W: The unfolded protein response is activated in Alzheimer’s disease. Acta Neuropathol 2005; 110: 165-172.
    Hoshino T, Nakaya T, Araki W, Suzuki K, Suzuki T, Mizushima T: Endoplasmic reticulum chaperones inhibit the production of amyloid-peptides. Biochem J 2007; 402, 581-589.
    Hsieh MC, Lin SR, Hsieh TJ, Hsu CH, Chen HC, Shin SJ, Tsai JH: Increased frequency of angiotensin-converting enzyme DD genotype in patients with type 2 diabetes in Taiwan. Nephrol Dial Transplant 2000; 15: 1008-1013.
    Huang HM, Kuo YM, Ou HC, Lin CC, Chuo LJ: Apolipoprotein E polymorphism in various dementias in Taiwan Chinese population. J Neural Transm 2002; 109: 1415-1421.
    Hunley TE, Julian BA, Philips JA III, Summar ML, Yoshida H, Horn RG, Brown NJ, Fogo A, Ichikawa I, Kon V: Angiotensin converting enzyme gene polymorphism: potential silencer motif and impact on progression in IgA nephropathy. Kidney Int 1996; 49: 571-577.
    Hye A, Lynham S, Thambisetty M, Causevic M, Campbell J, Byers HL, Hooper C, Rijsdijk F, Tabrizi SJ, Banner S, Shaw CE, Foy C, Poppe M, Archer N, Hamilton G, Powell J, Brown RG, Sham P, Ward M, Lovestone S: Proteome-based plasma biomarkers for Alzheimer’s disease. Brain 2006; 129: 3042-3050.
    Ida N, Hartmann T, Pantel J, Schroder J, Zerfass R, Forstl H, Sandbrink R, Masters CL, Beyreuther K: Analysis of heterogeneous A4 peptides in human cerebrospinal fluid and blood by a newly developed sensitive Western blot assay. J Biol Chem 1996; 271: 22908-22914.
    Jensen M, Basun H, Lannfelt L: Increased cerebrospinal fluid tau in patients with Alzheimer’s disease. Neurosci Lett 1995; 186: 189-191.
    Kakimura J, Kitamura Y, Takata K, Tsuchiya D, Taniguchi T, Gebicke-Haerter PJ, Smith MA, Perry G, Shimohama S: Possible involvement of ER chaperone Grp78 on reduced formation of amyloid- deposits. Ann N Y Acad Sci 2002; 977: 327-332.
    Kakiuchi C, Ishiwata M, Nanko S, Kunugi H, Minabe Y, Nakamura K, Mori N, Fujii K, Umekage T, Tochigi M, Kohda K, Sasaki T, Yamada K, Yoshikawa T and Kato T: Functional polymorphisms of HSPA5: possible association with bipolar disorder. Biochem Biophys Res Commun 2005; 336: 1136-1143.
    Kalman J, Juhasz A, Csaszar A, Kanka A, Rimanoczy A, Janka Z, Rasko I: Increased apolipoprotein E4 allele frequency is associated with vascular dementia in the Hungarian population. Acta Neurol Scand 1998; 98: 166-168.
    Kanai M, Matsubara E, Isoe K, Urakami K, Nakashima K, Arai H, Sasaki H, Abe K, Iwatsubo T, Kosaka T, Igeta Y, Ikeda Y, Amari M, Kawarabayashi T, Ishiguro K, Harigaya Y, Wakabayashi K, Okamoto K, Hirai S, Shoji M: Longitudinal study of cerebrospinal fluid levels of tau, A 1-40, and A 1-42(43) in Alzheimer’s disease: a study in Japan. Ann Neurol 1998; 44: 17-26.
    Kang J, Muller-Hill B: Differential splicing of Alzheimer’s disease amyloid A4 precursor RNA in rat tissues: Pre A4 (695) mRNA is predominantly produced in rat and human brain. Biochem Biophys Res Commun 1990; 166: 1192-1200.
    Kario K, Kanai N, Saito K, Nago N, Matsuo T, Shimada K: Ischemic stroke and the gene for angiotensin-converting enzyme in Japanese hypertensives. Circulation 1996; 93: 1630-1633.
    Katayama T, Imaizumi K, Honda A, Yoneda T, Kudo T, Takeda M, Mori K, Rozmahel R, Fraser P, St. George-Hyslop PS, Tohyama M: Disturbed activation of endoplasmic reticulum stress transducers by familial Alzheimer’s disease-linked presenilin-1 mutations. J Biol Chem 2001; 276: 43446-43454.
    Katayama T, Imaizumi K, Manabe T, Hitomi J, Kudo T, Tohyama M: Induction of neuronal death by ER stress in Alzheimer’s disease. J Chem Neuroanat 2004; 28: 67-78.
    Kawamata J, Tanaka S, Shimohama S, Ueda K, Kimura J: Apolipoprotein E polymorphism in Japanese patients with Alzheimer’s disease or vascular dementia. Neurol Neurosurg Psychiatry 1994; 57: 1414-1416.
    Keavney B, McKenzie CA, Connell JM, Julier C, Ratcliffe PJ, Sobel E, Lathrop M, Farrall M: Measured haplotype analysis of the angiotensin- I converting enzyme gene. Hum Mol Genet 1998; 7: 1745-1751.
    Kehoe PG, Russ C, McIlory 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.
    Ki CS, Na DL, Kim DK, Kim HJ, Kim JW: Lack of association of the interleukin-1gene polymorphism with Alzheimer’s disease in a Korean population. Ann Neurol 2001; 49: 817-818.
    Kitaguchi N, Takahashi Y, Okushima Y, Shiojiri S, Ito H: Novel precursor of Alzheimer’s disease amyloid protein shows protease inhibitory activity. Nature 1988; 331: 530-532.
    Ki CS, Na DL, Kim DK, Kim HJ, Kim JW: Lack of association of the interleukin-1 gene polymorphism with Alzheimer’s disease in a Korean population. Ann Neurol 2001; 49: 817-818.
    Kivipelto M, Helkala EL, Hanninen T, Laakso MP, Hallikainen M, Alhainen K, Soininen H, Tuomilehto J, Nissinen A: Midlife vascular risk factors and late-life mild cognitive impairment: a population-based study. Neurology 2001; 56: 1683-1689.
    Klebanoff SJ, Waltersdorph AM: Inhibition of peroxidase-catalyzed reactions by deferoxamine. Arch Biochem Biophys 1988; 264: 600-606.
    Kolsch H, Ptok U, Bagli M, Papassotiropoulos A, Schmitz S, Barkow K, Kockler M, Rao ML, Maier W, Heun R: Gene polymorphisms of interleukin-1alpha influence the course of Alzheimer’s disease. Ann Neurol 2001; 49: 818-819.
    Kolsch H, Jessen F, Freymann N, Kreis M, Hentschel F, Maier W, Heun R: ACE I/D polymorphism is a risk factor of Alzheimer’s disease but not of vascular dementia. Neurosci Lett 2005; 377: 37-39.
    Konig G, Monning U, Czech C, Prior R, Banatif R, Schreiter-Gasserll U, Bauerll J, Masters CL, Beyreuthe K: Identification and differential expression of a novel alternative splice isoform of the A4 amyloid precursor protein (APP) mRNA in leukocytes and brain microglial cells. J Biol Chem 1992; 267: 10804-10809.
    Kosik KS: Alzheimer’s disease: A cell biological perspective. Science 1992; 256: 780-783.
    Kuo YM, Emmerling MR, Lampert HC, Hempelman SR, Kokjohn TA, Woods AS, Cotter RJ, Roher AE: High levels of circulating A42 are sequestered by plasma proteins in Alzheimer’s disease. Biochem Biophys Res Commun 1999; 257: 787-791.
    Kuo YM, Liao PC, Lin C, Wu CW, Huang HM, Lin CC, Chuo LJ: Lack of association between interleukin-1polymorphism and Alzheimer’s disease or vascular dementia. Alzheimer Dis Assoc Disord 2003; 17: 94-97.
    Kurz A, Riemenschneider M, Buch K, Willoch F, Bartenstein P, Muller U, Guder W: Tau protein in cerebrospinal fluid is significantly increased at the earliest clinical stage of Alzheimer’s disease. Alzheimer Dis Assoc Disord 1998; 12: 372-377.
    Lai CL, Tai CT, Lin SR, Lin RT, Yang YH, Liu CK: Apolipoprotein E in Taiwan Chinese patients with dementia. Dement Geriatr Cogn Disord 2003; 16: 208-211.
    Lee AS: The glucose-regulated proteins: stress induction and clinical applications. Trends Biochem Sci 2001; 26(8): 504-510.
    Lee AS: The ER chaperone and signaling regulator GRP78/Bip as a monitor of endoplasmic reticulum stress. Methods 2005; 35(4): 373-381.
    Lee-Chen GJ, Liu KP, Lai YC, Juang HS, Huang SY, Lin CY: Significance of the tissue kallikrein promoter and transforming growth factor-1 polymorphisms with renal progression in children with vesicoureteral reflux. Kidney Int 2004; 65: 1467-1472.
    Levene H: On a matching problem in genetics. Ann Math Stat 1949; 20: 91-94.
    Levine RL: Oxidative modification of glutamine synthetase. I. Interaction is due to loss of one histidine residue. J Biol Chem 1983; 258: 11823-11827.
    Levy-Lahad E, Wasco W, Poorkaj P, Romano DM , Oshima J, Pettingell WH, Yu C-en, Jondro PD, Schmidt SD, Wang K, Crowley AC, Fu Y-H, Guenette SY, Galas D, Nemens E, Wijsman EM, Bird TD, Schellenberg GD, Tanzi RE: Candidate gene for the chromosome 1 familiar Alzheimer’s disease locus. Science 1995; 269: 973-977.
    Li WW, Hsiung Y, Zhou Y, Roy B, Lee AS: Induction of the mammalian GRP78/BiP gene by Ca2+ depletion and formation of aberrant proteins: activation of the conserved stress-inducible grp core promoter element by the human nuclear factor YY1. Mol Cell Biol 1997; 17: 54-60.
    Liu KP, Lin CY, Chen HJ, Wei CF, Lee-Chen GJ: Renin-angiotensin system polymorphisms in Taiwanese primary vesicoureteral reflux. Pediatr Nephrol 2004; 19: 594-601.
    Luca MD, Pastorino L, Bianchetti A, Perez J, Vignolo LA, Lenzi GL, Trabucchi M, Cattabeni F, Padovani A: Differential level of platelet amyloid precursor protein isoforms. Arch Neurol 1998; 55: 1195-1200.
    Maglione V, Giallonardo P, Cannella M, Martino T, Frati L, Squitieri F: Adenosine A(2A) receptor dysfunction correlates with age at onset anticipation in blood platelets of subjects with Huntington’s disease. Am J Med Genet B Neuropsychiatr Genet 2005; 139: 101-105.
    March CJ, Mosley B, Larsen A, Cerretti DP, Braedt G, Price V, Gillis S, Henney CS, Kronheim SR, Grabstein K, Conlon P, Hopp T, Cosman D: Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature 1985; 315: 641-647.
    Marcus N, Green M: NF-Y, a CCAAT box-binding protein, is one of the trans-acting factors necessary for the response of the murine ERp72 gene to protein traffic. DNA Cell Biol 1997; 16: 1123-1131.
    Margolis HS, Geller R, Pisano JJ, Sjoerdsma A: Altered urinary kallikrein excretion in human hypertension. Lancet 1971; 298: 1063-1065.
    Marin DB, Breuer B, Marin ML, Silverman J, Schmeidler J, Greenberg D, Flynn S, Mare M, Lantz M, Libow L, Neufeld R, Altstiel L, Davis KL, Mohs RC: The relationship between apolipoprotein E, dementia, and vascular illness. Atherosclerosis 1998; 140: 173-180.
    Markus HS, Barley J, Lunt R, Bland JM, Jeffery S, Carter ND, Brown MM: Angiotensin-converting enzyme gene deletion polymorphism: a new risk factor for lacunar stroke but not carotid atheroma. Stroke 1995; 26: 1329-1333.
    Masliah E, Mallory M, Hansen L, De Teresa R, Alford M, Terry R: Synaptic and neuritic alternations during the progression of Alzheimer’s disease. Neurosci Lett 1994; 174: 67-72.
    Matsubara E, Ghiso J, Frangione B, Amari M, Tomidokoro Y, Ikeda Y, Harigaya Y, Okamoto K, Shoji M: Lipoprotein-free amyloidogenic peptides in plasma are elevated in patients with sporadic Alzheimer’s disease and Down’s syndrome. Ann Neurol 1999; 45: 537-541.
    Mattila KM, Rinne JO, Lehtimaki T, Roytta M, Ahonen JP, Hurme M: Association of an interleukin 1B gene polymorphism (-889) with Parkinson’s disease in Finnish patients. J Med Genet 2002; 39: 400-402.
    McDowell TL, Symons JA, Ploski R, Forre O, Duff GW: A genetic association between juvenile rheumatoid arthritis and a novel interleukin-1polymorphism. Arthritis Rheum 1995; 38: 221-228.
    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 auspices of department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984; 34: 934-944.
    Molero AE, Pino-Ramirez G, Maestre GE: Modulation by age and gender of risk for Alzheimer’s disease and vascular dementia associated with the apolipoprotein E-epsilon4 allele in Latin Americans: findings from the Maracaibo Aging Study. Neurosci Lett 2001; 307: 5-8.
    Monning U, Konig G, Prior R, Mechler H, Schreiter-Gasser U, Masters CL, Beyreuther K: Synthesis and secretion of Alzheimer’s amyloid A4 precursor protein by stimulated human peripheral blood leucocytes. FEBS Lett 1990; 277: 261-266.
    Moroney JT, Bagiella E, Desmond DW, Hachinski VC, Molsa PK, Gustafson L, Brun A, Fischer P, Erkinjuntti T, Rosen W, Paik MC, Tatemichi TK: Meta-analysis of the Hachinski Ischemic Score in pathologically verified dementias. Neurology 1997; 49: 1096-1105.
    Morris BJ, Zee RY, Schrader AP: Different frequencies of angiotensin-converting enzyme genotypes in older hypertensive individuals. J Clin Invest 1994; 94: 1085-1089.
    Motter R, Vigo-Pelfrey C, Kholodenko D, Barbour R, Johnson-Wood K, Galasko D, Chang L, Miller B, Clark C, Green R, Olson D, Southwick P, Wolfert R, Munroe B, Lieberburg I, Seubert P, Schenk D: Reduction of –amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer’s disease. Ann Neurol 1995; 38: 643-648.
    Nagata E, Sawa A, Ross CA, Snyder SH: Autophagosome-like vacuole formation in Huntington’s disease lymphoblasts. Neuroreport 2004; 15: 1325-1328.
    Nakamura A and Goto S: Analysis of protein carbonyls with 2,4-dinitrophynyl hydrazine and its antibodies by immunoblot in two-dimensional gel electrophoresis. J Biochem 1996; 119: 768-774.
    Nalbantoglu J, Gilfix BM, Bertrand P, Robitaille Y, Gauthier S, Rosenblatt DS, Poirier J: Predictive value of apolipoprotein E genotyping in Alzheimer’s disease: results of an autopsy series and an analysis of several combined studies. Ann Neurol 1994; 36: 889-895.
    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.
    Nemetz A, Nosti-Escanilla MP, Molnar T, Kope A, Kovacs A, Feher J, Tulassay Z, Nagy F, Garcia-Gonzalez MA, Pena AS: IL1B gene polymorphisms influence the course and severity of inflammatory bowel disease. Immunogenetics 1999; 49: 527-531.
    Nicoll JA, Mrak RE, Graham DI, Stewart J, Wilcock G, MacGowan S, Esiri MM, Murray LS, Dewar D, Love S, Moss T, Griffin WS: Association of interleukin-1 gene polymorphisms with Alzheimer’s disease. Ann Neurol 2000; 47: 365-368.
    Nishimura M, Mizuta I, Mizuta E, Yamasaki S, Ohta M, Kuno S: Influence of interleukin-1 gene polymorphisms on age-at-onset of sporadic Parkinson’s disease. Neurosci Lett 2000; 284: 73-76.
    Nishimura M, Kuno S, Kaji R, Yasuno K, Kawakami H: Glutathione-S-transferase-1 and interleukin-1 gene polymorphisms in Japanese patients with Parkinson’s disease. Mov Disord 2005; 20: 901-902.
    Nothwang HG, Strahm B, Denich D, Kubler M, Schwabe J, Gingrich JC, Jauch A, Cox A, Nicklin MJ, Kurnit DM, Hildebrandt F: Molecular cloning of the interleukin-1 gene cluster: construction of an integrated YAC/ PAC contig and a partial transcriptional map in the region of chromosome 2q13. Genomics 1997; 41: 370-378.
    Nyholt DR: A simple correction for multiple testing for singlenucleotide polymorphisms in linkage disequilibrium with each other. Am J Hum Genet 2004; 74: 765-769.
    Oliver CN, Ahn B, Moerman EJ, Goldstein S, Stadtman ER: Age-related changes in oxidized protein. J Biol Chem 1987; 262: 5488-5491.
    Palumbo B, Cadini D, Nocentini G, Filipponi E, Fravolini ML, Senin U: Angiotensin converting enzyme deletion allele in different kinds of dementia disorders. Neurosci Lett 1999; 267: 97-100.
    Parker R, Phan T, Baumeister P, Roy B, Cheriyath V, Roy AL, Lee AS: Identification of TFII-I as the endoplasmic reticulum stress response element binding factor ERSF: its autoregulation by stress and interaction with ATF6. Mol Cell Biol 2001; 21: 3220-3233.
    Pognonec P, Kato H, Roeder RG: The helix-loop/leucine repeat transcription factor USF can be functionally regulated in a redox-dependent manner. J Biol Chem 1992; 267: 24563-24567.
    Rall SC Jr, Weisgraber KH, Mahley RW: Human apolipoprotein E. The complete amino acid sequence. J Biol Chem 1982; 257: 4171-4178.
    Rebeck GW: Confirmation of the genetic association of interleukin-1A with early onset sporadic Alzheimer’s disease. Neurosci Lett 2000; 293: 75-77.
    Rebeck GW, Perls TT, West HL, Sodhi P, Lipsitz LA, Hyman BT: Reduced apolipoprotein epsilon 4 allele frequency in the oldest old Alzheimer’s patients and cognitively normal individuals. Neurology 1994; 44: 1513-1516.
    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.
    Richard F, Fromentin-David I, Ricolfi F, Ducimetiere P, Di Menza C, Amouyel P, Helbecque N: The angiotensin I converting enzyme gene as a susceptibility factor for dementia. Neurology 2001; 56: 1593-1595.
    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.
    Rosenberg RN, Baskin F, Fosmire JA, Risser R, Adams P, Svetlik D, Honig LS, Cullum CM, Weiner MF: Altered amyloid protein processing in platelets of patients with Alzheimer disease. Arch Neurol 1997; 54: 139-144.
    Rogers JT, Leiter LM, McPhee J, Cahill CM, Zhan SS, Potter H, Nilsson LN: Translation of the alzheimer amyloid precursor protein mRNA is up-regulated by interleukin-1 through 5’-untranslated region sequences. J Biol Chem 1999; 274: 6421-6431.
    Roman GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, Amaducci L, Orgogozo JM, Brun A, Hofman A, Moody DM, O’Brien MD, Yamaguchi T, Grafman J, Drayer BP, Bennett DA, Fisher M, Ogata J, Kokmen E, Bermejo F, Wolf PA, Gorelick PB, Bick KL, Pajeau AK, Bell MA, DeCarli C, Culebras A, Korczyn AD, Bogousslavsky J, Hartmann A, Scheinberg P: Vascular dementia. Diagnostic criteria for research studies: report of the NINDSAIREN international workshop. Neurology 1993; 43: 250-260.
    Sanan DA, Weisgraber KH, Russell SJ, Mahley RW, Huang D, Saunders A, Schmechel D, Wisniewski T, Frangione B, Roses AD: Apolipoprotein E associates with beta amyloid peptide of Alzheimer’s disease to form novel monofibrils. Isoform apoE4 associates more efficiently than apoE3. J Clin Invest 1994; 94(2): 860-869.
    Sato N, Imaizumi K, Manabe T, Taniguchi M, Hitomi J, Katayama T, Yoneda T, Morihara T, Yasuda Y, Takagi T, Kudo T, Tsuda T, Itoyama Y, Makifuchi T, Fraser PE, St George-Hyslop P, Tohyama M: Increased production of -amyloid and vulnerability to endoplasmic reticulum stress by an aberrant spliced form of presenilin 2. J Biol Chem 2001; 276: 2108-2114.
    Saunders AM, Strittmatter WJ, Schmechel D, George-Hyslop PH, Pericak-Vance MA, Joo SH, Rosi BL, Gusella JF, Crapper- MacLachlan DR, Alberts MJ: Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer’s disease. Neurology 1993; 43(8): 1467-1472.
    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.
    Schroder M, Kaufman RJ: ER stress and the unfolded protein response. Mutat Res 2005; 569: 29-63.
    Selkoe DJ: Translating cell biology into therapeutic advances in Alzheimer’s disease. Nature 1999; 399: A23-A31.
    Selkoe DJ, Podlinsly MB, Joakim CL: Beta-amyloid precursor protein of Alzheimer’s disease occurs as 110- to 135-kilodalton membrane associated proteins in neural and non-neural tissues. Proc Natl Acad Sci USA 1988; 85: 7341-7345.
    Shacter E, Williams JA, Lim M, Levine RL: Differential susceptibility of plasma proteins to oxidative modification: examination by western blot immunoassay. Free Radic Bio Med 1994; 17: 429-437.
    Sharma P, Carter ND, Barley J, Brown MM: Molecular approach to assessing the genetic risk of cerebral infarction: deletion polymorphism in the gene encoding angiotensin 1-converting enzyme. J Hum Hypertens 1994; 8: 645-648.
    Shayo M, McLay RN, Kastin AJ, Bands WA: The putative blood-brain barrier transporter for the -amyloid binding protein apolipoprotein J is saturated at physiological concentrations. Life Sci 1997; 60: PL115-PL118.
    Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K, Tsuda T, Mar L, Foncin J-F, Bruni AC, Montesi MP, Sorbi S, Rainero I, Pinessi L, Nee L, Chumakov I, Pollen D, Brookes A, Sanseau P, Polinsky RJ, Wasco W, Da Silva HAR, Haines JL, Pericak-Vance MA, Tanzi RE, Roses AD, Fraser, PE, Rommens JM, St George-Hyslop PH: Cloning of a gene bearing missense mutations in early-onset familiar Alzheimer’s disease. Nature 1995; 375: 754-760.
    Shigenaga MK, Gimeno CJ, Ames BN: Urinary 8-hydroxy-2’- deoxyguanosine as a biological marker of in vivo oxidative DNA damage. Proc Natl Acad Sci USA 1989; 86: 9697-9701.
    Shimano H, Ishibashi S, Murase T, Gotohda T, Yamada N, Takaku F, Ohtomo E: Plasma apolipoproteins in patients with multi-infarct dementia. Atherosclerosis 1989; 79(2-3): 257-60.
    Shiozaki A, Tsuji T, Kohno R, Kawamata J, Uemura K, Teraoka H, Shimohama S: Proteome analysis of brain proteins in Alzheimer’s disease: subproteomics following sequentially extracted protein preparation. Journal of Alzheimer’s Disease 2004; 6: 257-268.
    Siest G, Pillot T, Regis-Bailly A, Leininger-Muller B, Steinmetz J, Galteau MM, Visvikis S: Apolipoprotein E: an important gene and protein to follow in laboratory medicine. Clin Chem 1995; 41(8 Pt 1): 1068-1086.
    Simonsen AH, McGuire J, Podust VN, Davies H, Minthon L, Skoog I, Andreasen N, Wallin A, Waldemar G, Blennow K: Identification of a novel panel of cerebrospinal fluid biomarkers for Alzheimer’s disease. Neurobiol Aging 2008; 29: 961-968.
    Slooter AJ, Tang MX, van Duijn CM, Stern Y, Ott A, Bell K, Breteler MM, Van Broeckhoven C, Tatemichi TK, Tycko B, Hofman A, Mayeux R: Apolipoprotein E epsilon4 and the risk of dementia with stroke. A population-based investigation. JAMA 1997; 277: 818-821.
    Smith CD, Carney JM, Starke-Reed PE, Oliver CN, Stadtman ER, Floyd RA, Markesbery WR: Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer’s disease. Proc Natl Acad Sci USA 1991; 88: 10540-10543.
    Sobel E, Louhija J, Sulkava R, Davanipour Z, Kontula K, Miettinen H, Tikkanen M, Kainulainen K, Tilvis R: Lack of association of apolipoprotein E allele epsilon 4 with late-onset Alzheimer’s disease among Finnish centenarians. Neurology 1995; 45(5): 903-907.
    Song Q, Chao J, Chao L: DNA polymorphisms in the 50-flanking region of the human tissue kallikrein gene. Hum Genet 1997; 99: 727-734.
    Stadtman ER: Oxidation of proteins by mixed-function oxidation systems: implication in protein turnover, ageing and neutrophil function. Trends Biochem Sci 1986; 11: 11-12.
    Stadtman ER: Metal ion-catalyzed oxidation of proteins: biochemical mechanism and biological consequences. Free Radic Biol Med 1990; 9: 315-325.
    Stadtman ER: Protein oxidation and aging. Science 1992; 257: 1220-1224.
    Stadtman ER, Barlett BS: Fenton chemistry. Amino acid oxidation. J Biol Chem 1991; 266: 17201-17211.
    Stephens M, Smith NJ, Donnelly P: A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 2001; 68: 978-989.
    Stief TW, Marx R, Heimburger N: Oxidized fibrin(ogen) derivatives enhance the activity of tissue type plasminogen activator. Thromb Res 1989; 56: 221-228.
    Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, Roses AD.: Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci USA 1993; 90(5): 1977-1981.
    Strittmatter WJ, Weisgraber KH, Goedert M, Saunders AM, Huang D, Corder EH, Dong LM, Jakes R, Alberts MJ, Gilbert JR: Hypothesis: microtubule instability and paired helical filament formation in the Alzheimer disease brain are related to apolipoprotein E genotype. Exp Neurol 1994;125(2): 163-171; discussion 172-174.
    Strohmeyer R, Rogers J: Molecular and cellular mediators of Alzheimer’s disease inflammation. J Alzheimer Dis 2001; 3: 131-157.
    Sunderland T, Gur RE, Arnold SE: The use of biomarkers in the elderly: current and future challenges. Biol Psychiatry 2005; 58: 272-276.
    Tang K, Hynan LS, Baskin F, Rosenberg RN: Platelet amyloid precursor protein processing: a bio-marker for Alzheimer’s disease. J Neurol Sci 2006; 240: 53-58.
    Tanzi RE, McClatchey AJ, Lamperti ED, Villa-Komaroff L, Gusella, Neve RL: Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer’s disease. Nature 1988; 331: 528-530.
    Tapiola T, Overmyer M, Lehtovirta M, Helisalmi S, Ramberg J, Alafuzoff I, Riekkinen P, Soininen H: The level of cerebrospinal fluid tau correlates with neurofibrillary tangles in Alzheimer’s disease. Neuroreport 1997; 8: 3961-3963.
    Tarkowski E, Liljeroth AM, Nilsson A, Minthon L, Blennow K: Decreased levels of intrathecal interleukin 1 receptor antagonist in Alzheimer’s disease. Dement Geriatr Cogn Disord 2001; 12: 314-317.
    Tsai SJ, Liu HC, Liu TY, Wang KY, Hong CJ: Lack of association between the interleukin- 1alpha gene C(-889)T polymorphism and Alzheimer’s disease in a Chinese population. Neurosci Lett 2003; 343: 93-96.
    Utermann G, Langenbeck U, Beisiegel U, Weber W: Genetics of the apolipoprotein E system in man. Am J Hum Genet 1980; 32(3): 339-347.
    van Duijn CM, de Knijff P, Cruts M, Wehnert A, Havekes LM, Hofman A, Van Broeckhoven C: Apolipoprotein E4 allele in a population-based study of early-onset Alzheimer’s disease. Nat Genet 1994; 7: 74-78.
    Vattemi G, Engel WK, McFerrin J, Askanas V: Endoplasmic reticulum stress and unfolded protein response in inclusion body myositis muscle. Am J Pathol 2004; 164: 1-7.
    Villard E, Tiret L, Visvikis S, Rakotovao R, Cambien F, Soubrier F: Identification of new polymorphisms of the angiotensin I-converting enzyme (ACE) gene, and study of their relationship to plasma ACE levels by two-QTL segregation-linkage analysis. Am J Hum Genet 1996; 58: 1268-1278.
    Wang WF, Liao YC, Wu SL, Tsai FJ, Lee CC, Hua CS: Association of interleukin-I beta and receptor antagonist gene polymorphisms with late onset Alzheimer’s disease in Taiwan Chinese. Eur J Neurol 2005; 12: 609-613.
    Weisgraber KH, Rall SC Jr, Mahley RW: Human apolipoprotein E heterogeneity. Cysteine-arginine interchanges in the amino acid sequence of the apo E isoforms. J Biol Chem 1981; 256: 9077-9083.
    Weitzman SA, Gordon LI: Inflammation and cancer: role of phagocyte-generated oxidants in carcinogenesis. Blood 1990; 76: 655-663.
    Wisniewski T, Golabek A, Matsubara E, Ghiso J, Frangione B: Apolipoprotein E: binding to soluble Alzheimer’s beta-amyloid. Biochem Biophys Res Commun 1993; 192(2): 359-365.
    Wolff SP, Dean RT: Fragmentation of proteins by free radicals and its effect on their susceptibility to enzymic hydrolysis. Biochem J 1986; 234: 399-403.
    Wyss-Coray T, Mucke L: Inflammation in neurodegenerative disease – a double-edged sword. Neuron 2002; 35: 419-432.
    Yan SD, Fu J, Soto C, Chen X, Zhu H, Al-Mohanna F, Collison K, Zhu A, Stern E, Saido T et al.: An intracellular protein that binds amyloid- peptide and mediates neurotoxicity in Alzheimer’s disease. Nature 1997; 389: 689-695.
    Yang Y, Turner RS, Gaut JR: The chaperone BiP/GRP78 binds to amyloid precursor protein and decreases A40 and A42 secretion. J Biol Chem 1998; 273, 25552–25555.
    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.
    Yeh FC, Boyle T (1997) Population genetic analysis of codominant and dominant markers and quantitative traits. Belgian J Botang 1997: 129-157.
    Yoo BC, Kim SH, Cairns N, Fountoulakis M, Lubec G: Deranged expression of molecular chaperones in brains of patients with Alzheimer’s disease. Biochem Biophys Res Commun 2001; 280: 249-258.
    Yoshida H, Haze K, Yanagi H, Yura T, Mori K: Identification of the cis-acting endoplasmic reticulum stress response element responsible for transcriptional induction of mammalian glucoseregulated proteins. Involvement of basic leucine zipper transcription factors. J Biol Chem 1998; 273: 33741-33749.
    Yoshikai S, Sasaka H, Doh-ura K, Furuya H, Sasaki Y: Genomic organization of the human amyloid beta protein precursor gene. Gene 1990; 87: 257-263.
    Yu H, Song Q, Freedman BI, Chao J, Chao L, Rich SS, Bowden DW: Association of the tissue kallikrein gene promoter with ESRD and hypertension. Kidney Int 2002; 61: 1030-1039.
    Yucesoy B, Peila R, White LR, Wu KM, Johnson VJ, Kashon ML, Luster MI, Launer LJ: Association of interleukin-1 gene polymorphisms with dementia in a communitybased sample: the Honolulu-Asia Aging Study. Neurobiol Aging 2006; 27: 211-217.
    Zee RY, Lou YK, Griffiths LR, Morris BJ: Association of a polymorphism of the angiotensin I-converting enzyme gene with essential hypertension. Biochem Biophys Res Commun 1992; 184: 9-15.
    Zetterberg H, Ruetschi U, Portelius E, Brinkmalm G, Andreasson U, Blennow K, Brinkmalm A.: Clinical proteomics in neurodegenerative disorders. Acta Neurol Scand 2008; 118: 1-11.
    Zhang R, Barker L, Pinchev D, Marshall J, Rasamoelisolo M, Smith C, Kupchak P, Kireeva I, Ingratta L, Jackowski G: Mining biomarkers in human sera using proteomic tools. Proteomics 2004; 4: 244-256.
    Zhang J, Goodlett DR, Quinn JF, Peskind E, Kaye JA, Zhou Y, Pan C, Yi E, Eng J, Wang Q, Aebersold RH, Montine TJ: Quantitative proteomics of cerebrospinal fluid from patients with Alzheimer disease. J Alzheimer’s Dis 2005; 7: 125-133.
    Zuliani G, Ble’ A, Zanca R, Munari MR, Zurlo A, Vavalle C, Atti AR, Fellin R: Genetic polymorphisms in older subjects with vascular or Alzheimer’s dementia. Acta Neurol Scand 2001; 103: 304-308.

    下載圖示
    QR CODE