血液流變學的研究在臨床醫學應用之發展上具有舉足輕重的影響。近年來阿滋海默症病患體內微循環障礙的病理徵象，漸為臨床醫師所重視。本研究主要以血液流變學(Hemorheology)模式評估阿滋海默症(Alzheimer’s disease)老人各項血液流變參數的異常，並討論血液流變參數異常的機制及其對於阿滋海默症老人體內微循環的影響。
研究對象以 6位阿滋海默症老人為實驗組及10位年齡與實驗組相近的正常老人為對照組。兩組受測者以簡易智能狀態測驗(MMSE ; Minimurn Mental State Examination)以評估患者認知功能。經空腹採血進行血液各項生化、血球及血液流變參數檢測。分別於低、中及高剪切率下檢測全血黏度(Whole Blood Viscosity)，震盪流中檢測黏彈性(Blood Viscoelasticity)，低剪切率下測定紅血球聚集度(Erythrocyte Aggregation)，高剪切率下檢測紅血球變形度(Erythrocyte Deformability)及血漿黏度(Plasma Viscosity)，及利用Dintenfass所提之公式{Tk= [(ηr0.4-1)/ηr0.4 ] / Hct}計算出紅血球內黏度(Tk Level )。
實驗結果顯示，阿滋海默症老人血液流變各項參數，從巨觀之血液黏度至微觀之紅血球變形度皆顯著異常於正常老人。其中阿滋海默症老人之血液黏度、血漿黏度、血漿纖維蛋白原、血液黏彈性及紅血球聚集度皆明顯高於正常老人，而紅血球變形度則明顯低於正常老人。然而紅血球容積比與紅血球內黏度並無明顯差異。而引起阿滋海默症老人血液中紅血球於低剪切率下表現出高聚集性，使血液黏度增高，其主因為血漿中纖維蛋白原增高。於高剪切率下表現出低變形度，使血液黏度增加則主因於紅血球膜性質的改變之故。

Hemorheological studies were very important in the clinical development. Recently,microvascular abnormalities in Alzheimer’s disease is under intensive investigated.This study to evaluate the changes in hemorheological indexes for patients with Alzheimer’s disease and to discuss the mechanism of these changes and the effects in patients with Alzheimer’s disease.
Six elderly patients with Alzheimer’s disease and ten age-matched healthy subjects were included by evaluating the cognitive function of the Minimum Mental State Examination test (MMSE) . Fasting blood samples were collected to measure the biochemistries, complete blood counts and hemorheological indexes. Whole blood viscosity was measured in low, middle and high shear rate. Blood viscoelasticity was measured in oscillated model, Moreover,erythrocyte aggregation was measured in low shear rate.And plasma viscosity and erythrocyte deformability were measured in high shear. “Tk”level was calculated according to the equation {Tk= [(ηr0.4-1)/ηr0.4 ] / Hct } of Dintenfass.
The result revealed that there were significant different in all hemorheological indexes between Alzheimer’s disease group and control group except Hct and Tk level. Whole blood viscosity, plasma viscosity, viscoelasticity, plasma fibrinogen and erythrocyte aggregation of patients with Alzheimer’s disease group were significant higher than those of normal control group.Erythrocyte deformability of patients with Alzheimer’s disease was significant lower than healthy subjects. The increased erythrocyte aggregation duing low shear rate may due to the increased fibrinogen concentration.The decreased erythrocyte de- formability during high shear rate may result from membrane modification of erythrocyte.

目 錄
謝 誌……………………………………………………………………一
中 文 摘 要……………………………………………………………二
英 文 摘 要……………………………………………………………三
目 錄…………………………………………………………………....四
圖 表 索 引………………………………………………...………….七
第 壹 章 緒論………………………………………………………....1
§ 1 — 1 阿滋海默症的發生……………………………………..……..3
1-1-1 阿滋海默症之病理進展………………………………….…...5
1-1-2 阿滋海默症臨床上異常的表現…………………….………..8
§ 1 — 2 文獻回顧與研究目的………………………………………...10
§ 1 — 3 血液流變學參數……………………………………………...14
一. 黏度………………………………………………………………....14
二. 血漿黏度………………………………………………………. …..16
三. 血液黏度…………………………………………………………....16
四. 物體黏彈性及黏彈流體之介紹…………………………………....19
五. 血液的黏彈流體特性及其影響因素……………………………....19
六. 紅血球變形與量測原理…………………………………………....22
七. 紅血球聚集性與量測原理………………………………………....25
§ 1 — 4 紅血球的生化結構………………………………………..….28
(一). 紅血球膜之組成及結構………….……………………………....28
(二). 紅血球的內成分…………………..……………………………...34
(三). 紅血球的形狀和生化基礎…………………..…………………...36
§ 1 — 5 類澱粉蛋白(β-amyloid protein)的介紹及其臨床意義……...38
一. 類澱粉蛋白的來源………………………………………………...38
二. 類澱粉蛋白的作用………………………………………………...40
第貳章 實驗設備與方法……………………………………………..43
§ 2 — 1 實驗設備……………………………………………………..43
一. 黏度計……………………………………………43
二. 自動水浴溫度控制器……………………………52
三. 自動血球計數分析儀……………………………52
四. 離心機……………………………………………53
五. 紅血球變形及聚集測試儀………………………54
六. 血清生化分析儀………………………………….60
七. 比濁法…………………………………………….60
§ 2 — 2 實驗方法與步驟………………………………..…………...61
§ 2 — 3 實驗流程圖…………………………...……………………..69
第參章 結果…………………………………………………………..70
第肆章 .討論………………………………………………………….77
第伍章 結論與未來展望……………………………………………..85
參考資料………………………………………………………………..88附錄 : 實驗數據………………………………………………………….
圖 表 索 引
圖 1 — 1 : 腦部在早期阿滋海默症受到侵襲的部位…………………...6
圖 1 — 2 : 腦萎縮與阿滋海默症…………………………………….…..7
圖 1 — 3 - a : 阿滋海默症老人腦部微血管之側觀……………………14
圖 1—3—b: 正常老人(A)及阿滋海默症老人(B)腦部微血管之cell free layer與神經元(neuron)間營養物質輸送示意圖….14
圖 1 — 4 : 紅血球膜及骨架之分子模型………………………………32
圖 1 — 5 : β-amyloid(Aβ) plaque的由來……………………………43
圖 2 — 1 : Rotational rheometer RS-I 黏度計之外觀圖………………....48
圖 2 — 2 : 2˚ 之double cone/plate 之 sensor圖……………………..…..49
圖 2 — 3 : Hct = 40% 的血液於不同剪切率下的黏度值(RS-I量測, 操作溫度37˚C , shear rate : 500 ~ 1 )……………...50
圖 2 — 4: Hct = 40% 的血液於固定形變(5%) , 不同頻率(0.2 ~ 5.0 Hz)下之黏彈性參數值(RS-I量測, 操作溫度37˚C )………….…51
圖 2 — 5: 血漿於37˚C , shear rate : 500 下之黏度值…………….52
圖 2 — 6: LG-B-190 Ektacytometer 紅血球變形.聚集分析儀之外觀圖……………………………………………………………...56
圖 2 — 7: LG-B-190 Ektacytometer 紅血球變形.聚集分析儀之升降頭角度范圍顯示及檢體置放旋轉盤板之側觀圖………………...57
圖 2 — 8: LG-B-190 Ektacytometer 紅血球變形.聚集分析儀之升降頭近觀圖…………………………………………………………...58
圖 2 — 9: LG-B-190 Ektacytometer 紅血球變形.聚集分析儀之雷射激光源與檢體置放區顯示圖……………………………………………….59
圖 2- 10: LG-B-190 Ektacytometer 紅血球變形.聚集分析儀之sensor
圖………………………………………………………………………..60
圖 2-11: 紅血球變形測試圖…………………………………………..65
圖 2-12: 紅血球聚集曲線圖…………………………………………..67
表 3 — 1: 阿滋海默症老人與正常老人之臨床生化特性…………….74
表 3 — 2: 阿滋海默症老人與正常老人之血液常規參數…………….75
表 3 — 3: 阿滋海默症老人與正常老人之血液流變參數…………….76

參考資料
1. Z.Wen , J.Xie , Z.W.Guan , D.Sun , W.Yao , K.Chen , Z.Yan and Q. Mu ,“A study of hemorheological behaviour fo patients with Alzheimer’s disease at the early stages”, Clinical Hemorheology and Microcirculation , 22 , 261-266 (2000)
2. R.P.Mayo : Clinic on Alzheimer’s Disease. Mayo Ch.4 (2003)
3. J.Hardy and D.Allsop ,“Amyloid deposition as the central event in the aetiology of Alzheimer’s disease”, Trends in Pharmacological Sciences , 12, 383-388 (1991)
4. D.Kogure , H.Matsuda , T.Ohnishi , T.Asada , M.Uno , T.Kunihiro , S. Nakano , and M.Takasaki ,“Longitudinal evaluation of early Alzheimer’s Disease using brain perfusion SPECT”, The Journal of Nuclear Medicine , 41 , 1155-1162 (2000)
5. J.C.Torre ,“Impaired brain microcirculation may trigger
Alzheimer’s Disease”, Neuroscience and biobehavioral Reviews , 18(3) , 397-401 (1994)
6. J.C.Torre and T.Mussivand ,“Can disturbed brain
microcirculation cause Alzheimer’s disease?”, Neurological Research , 15 , 146-153 (1993)
7. J.C.Torre,“Cerebromicrovascular pathology in Alzheimer’s disease compared to normal aging”, Gerontology , 43 , 26-43 (1997)
8. R.N.Kalaria,“Cerebral vessels in ageing and Alzheimer’s
Disease”, Pharmacology & Therapeutics , 72 , 193-214 (1996)
9. R.S.Ajmani , E.J.Metter , R.Jaykumar , D.K.Ingram , E.L.Spangler , O.O.Abugo , J.M.Rifkind , “Hemodynamic changes during aging associated with cerebral blood flow and impaired cognitive function”, Neurobiology of Aging , 21 , 257-269 (2000)
10.W.Meier-Ruge , C.Bertoni-Freddari , P.Iwangoff ,“Changes in
Brain glucose meatabolism as a key to the pathogenesis of Alzheimer’s disease”, Gerontology , 40 , 246-252 (1994)
11.J.J.Kremer , D.J.Sklansky , and R.M.Murphy ,
“Profile of changes in lipid bilayer structure caused byβ-amyloid peptide”, Biochemistry , 40 , 8563-8571 (2001)
12.M.A.Smith , L.M.Sayre , V.M.Monnier and G.Perry ,“Radical Ageing in Alzheimer’s disease”, Trends in Neurosciences , 18 , 172-176 (1995)
13.S.B.Solert , G.Ceresini , E.Ferrari , M.Fioravanti ,
“Hemorheological changes and overproduction of cytokines from immune cells in mild to moderated ementia of the Alzheimer’s type：adverse effects on cerebromicrovascular system”, Neurobiology of Aging , 21 , 271-281 (2000)
14.H.Chmiel , I.Anadere and E.Walitza, “The determination of blood
Viscoelasticity in clinical hemorheology”, Biorheology , 27 , 883-894 (1990)
15.M.S.Wolfe ,“Secretase targets for Alzheimer’s Disease：
Identification and therapeutic potential”, Journal of Medicinal Chemistry , 44(13) , 2039-2060 (2001)
16.A.M.Palmer ,“Pharmacotherapy for Alzheimer’s disease：
Progress and prospects”, Trends in Pharmacological Sciences , 23 , 426-433 (2002)
17.Y.Christen ,“Oxidative stress and Alzheimer disease” , American Journal of Clinical Nutrition, 71(suppl)：621S-629S (2000)
18. K.Ando , M.Beppu , K.Kikugawa , R.Nagai , and S.Horiuchi , “Membrane proteins of human erthrocytes are modified by advanced glycation end products during aging in the circulation”, Biochemical and Biophysical Research Communications , 258 , 123-127 (1999)
19.B.H.Choi ,“Oxidative stress and Alzheimer’s Disease”, Neruobiology of Aging , 16 , 675-678 (1995)
20. A.S.Henderson ,“The risk factors for Alzheimer’s disease：are view and a hypothesis”, Acta Psychiatr Scand , 78 , 257-275 (1998)
21. H.Lin , Y.J.Zhu , and R.Lal , “Amyloid βProtein(1-40) Forms Calcium-Permeable , Zn2+-Sensitive Channelin Reconstituted Lipid Vesicles”, Biochemistry , 38 , 11189-11196 (1999)
22.F.I.Braginskaya , O.M.Zorina , N.P.Pal’mina , V.D.Gaintseav , E.B.Burlakova , N.D.Selezneva , I.V.Kolykhalov , and S.I.Gavrilova , “Some blood biochemistry parameters during the cholinergic treatment of Alzheimer’s disease”, Neuroscience and Behavioral Physiology , 31 , 457-461 (2001)
23.D.Sabolovic’ , M.Roudier , M.Boynard , C.Pautou , C.Sestier , B. Fertil , D.Geldwerth , J.Roger , J.N.Pons , A.Amri , and A.Halbreich , “Membrane modifications of red blood cells in Alzheimer’s Disease”, Journal of Gerontology：Biological Sciences , 52a(4) , B217-B220 (1997)
24. J.J.Kremer , M.M.Pallitto , D.J.Sklansky , and R.M.Murphy ,“Correlationof β-amyloid aggregate size and hydrophobicity with decreased” , Biochemistry , 39 , 10309-10318 (2000)
25.G.B.Thurston ,“Rheological parameters for the viscosity viscoelasticity and theixotropy of blood” , Biorheology , 16 , 149-162 (1979)
26. T.C.Pearson and F.R.C.Path ,“Hoemorheology in the
erythrocytoses”, The Mount Sinai Journal of Medicine , 68(3) , 182-191 (2001)
27. G.J.C.G.M.Bosman , J.G.E.Janzing , I.G.P.Bartholmeus , A.J.M.Man , F.G.Zitman and W.J.Grip ,“Erythrocyte aging characteristics in elderly individuals with beginning dementia”, Neurobiology of aging , 18 , 291-295 (1997)
28. S.B.Solerte , M.Fioravanti , A.Pascale , E.Ferrari , S.Govoni and F.
Battaini ,“Increased natural killer cell cytotoxicity in Alzheimer’s disease may involve proteinkinase C dysregulation”, Neurobiology of Aging , 19 , 191-199 (1998)
29. A.M.Palmer and M.A.Burns ,“Selective increase in lipid
Peroxidation in the inferior temporal cortex in Alzheimer’s disease”, Brain Research , 645 , 338-342 (1994)
30. T.M.Fischer , C.W.M.Haest , M.Stohr , D.Kamp and B.Deuticke ,
“Selective alteration of erythrocyte deformability by shreagents evidence for an involvement of spectrin in membrane shear elasticity”, Biochimica et Biophysica Acta , 510 , 270-282 (1978)
31. D.E.McMillan , J.Strigberger , and N.G.Utterback ,“Rapidly recovered transient flow resistance : a newly discovered property of blood”, The American Physiological Sociaty , 87 , 919-926 (1987)
32. M.Huberman , F.Shalit , I.Roth-Deri , B.Gutman , C.Brodieb ,
E.kott , and B.Sredni ,“Correlation of cytokine
Secretion by mononuclear cells of Alzheimer patients and their disease stage”, Journal of Neuroimmunology , 52 , 147-152 (1994)
33.J.F.Stoltz and M.Lucius ,“Viscoelasticity and thixotropy of human blood”, Biorheology , 18 , 453-473 (1981)
34. D.Schneditz , V.Ribitsch and T.Kenner ,“Rheological
Discrimination between native , rigid and aggregated red blood cells in oscillatory flow”, Biorheology , 22 , 209-219 (1985)
35.A.Rakow , S.Simchon , L.A.Sung and S.Chien ,“Aggrgation of red cells with membrane altered by heat treatment”, Biorheology , 18 , 3-8 (1981)
36.S.Usami ,“Developmen to fhe morheology：perspecitve in
Instrumentation development”, Clinical Hemorheology and Microcirculation , 23 , 77-83 (2000)
37.J.Y.A.Lehtonen , J.M.Holopainen , and P.K.J.Kinnunen ,“Activation of phospholipase A2 by amyloidβ-peptides in vitro”,
Biochemistry , 35 , 9407-9414 (1996)
38.Z.Suo , J.Humphrey , A.Kundtz , F.Sethi , A.Placzek , F.Crawford and M.Mullan , “Soluble Alzheimersβ-amyloid constricts the cerebral vasculature in vivo“, Neruoscience Letters , 257 , 77-80 (1998)
39.RS-1 黏度儀操作說明書。HAAKE . 德國。2002
40.J.A.Schwartz , B.A.Keagy , and G.Johnson ,“Determination of whole blood apparent viscosity：Experience with a new hemorheologic technique”, Journal of Surgical Research , 45 , 238-247 (1988)
41.K.Kon , N.Maeda , and T.Shiga ,“Erythrocyte deformation in shear Flow：Influences of internal viscosity , membrane stiffness , and hematocrit”, Blood , 69 , 727-734 (1987)
42. L.B.Nanninga and M.M.Guest ,“Bloodviscosity；influence of erythrocyte aggregation“, Science , 157 , 829-831 (1967)
43. S.O.Sowemimo-Coker , G.Yardin and H.J.Meiselman ,“Effect of
Procaine hydrochloride on the aggregation behavior and suspension viscoelasticity of human red blood cells”, Biorheology , 26 , 951-972 (1989)
44.R.E.Wells , T.H.Gawronski , P.J.Cox , and R.D.Perera ,“Influence of fibrinogen on flow properties of erythrocyte suspensions”, American Journal of Physiology. , 207(5) , 1035-1040 (1964)
45.J.F.Stoltz , M.Singh and P.Riha ,“Hemorheology in Practice”, IOS Press Ch.3,Ch.4；Volue30 (1999)
46.D.Schneditz , F.Rainer and T.Kenner ,“Viscoelastic properties of
blood. Influence of fast sedimenting red blood cell aggregates”, Biorheology , 24 , 13-22 (1987)
47.P.C.Elwood , J.Pickering and J.E.J.Gallacher“Cognitive function and blood rheology：results from the caerphilly cohort of older men”, Age and Ageing , 30 , 135-139 (2001)
48.LG-B-190 紅血球聚集和變形儀操作說明書。 Ektacytometer. 2002
49.W.J.Drasler , C.M.SmithII , and K.H.Keller ,“Viscoelasicity of packed erythrocyte suspensions subjected to low amplitude oscillatiryde formability”, Biophysic Journal , 52 , 357-365 (1987)
50.F.C.Mokken , M.Kedaria , C.P.Henny , M.R.Hardemar , and A.W.Gelb ,“The clinical importance of erythrocyte deformability a
hemorheological parameter”, Annals of He matol , 64 , 113-122 (1992)
51. A.L.Copley , R.G.King , S.Chine , S.Usami , R.Skalak and
C.R.Huang ,“Microscopic observations of viscoelasticity of human blood in steady and oscillatolry shear”, Biorheology , 12 , 257-263 (1975)
52.劉士榮：高分子流變學,第六章,1995
53. L.Dintenfass“Internal viscosity of the red cell and a blood
viscosity equation”, Nature , 219 , 956-958 (1992)
54. R.S.Schwartz , J.W.Madsen , A.C.Rybick i, and R.L.Nagel ,“Oxidation of spectrin and deformability defects in diabetic erythrocytes”, Diabetes , 640 , 701-708 (1991)
55. B.D.Riquelme , P.G.Foresto , J.R.Valverde and J.R.Rasia ,
“Alterations to complex viscoelasticity of erythrocytes during storage”, Clinical Hemorheology and Microcirculation, 22,181-188 (2000)
56. G.Mchedlishvili , N.Beritashvili , D.Lominadze and B.T.Dzvrishvili ,“Technique for direct and quantitative evalution of erythrocyte aggregability in blood samples”, Biorheology , 30 , 153-161 (1993)
57. D.Danon , N.B.Bologna and S.Gavendo , “Memory performance of young and old subjects related to their erythrocyte characteristics”, Experimental Gerontology , 27 , 275-285 (1992)
58. G.B.Nash , R.Tran-Son-Tay and H.J.Meiselan , “Influence of preparative procedures on the membrane viscoelasticity of human red cell ghosts”, Biochimica et Biophysica Acta , 855 , 105-114 (1986)
59. 林榮耀,陳正宗:生物化學指引第九章,南山堂出版社,1999
60. RS-I黏度儀操作說明書.HAAKE.German.2002
61. X.Wang , H.Zhao , F.Y.Zhuang and J.F.Stoltz , “Measurement of erythrocyte deformability by two laser diffraction methods”, Clinical Hemorheology and Microcirculation , 21:291-295 (1999)
62. M.R.Clark ,“Osmotic gradient ektacytometry: Comprehensive
Characterization of red cell volume and surface maintenance”, Blood , 61(5) , 899-903 (1983)
63. I.Anadere , H.Chmiel and S.Witte ,“Hemorheological findings in
Patients with completed stroke and the influence of aginkgo biloba extract”, ClinicalHemorheology , 5 , 411-420(1985)
64. M.M.Brown and J.Marshall , “Regulation of cerebral blood flow in response to changes in blood viscosity”, The Lancet , 16 , 604-609 (1985)
65. L.M. Refolo , M.A. Pappolla and M.Betal , “Hypercholesterolemia accelerates the Alzheimer’s amyloid pathology inatransgenic mouse model”, Neurobiol Dis , 7 , 321-331 (2000)
66. J.J.Kremer , M.M.Pallitto , D.J.Sklansky , and R.M.Murphy ,“Correlation of β-amyloid aggregatesize and hydrophobicity with decreased bilayer fluidity of model membrane”, Biochemistry , 39 , 10309-10318 (2000)
67. H.Lechner , E.Ott and R.Schmidt , “Present state of hemorheology”, Gerontology , 33 , 259-264 (1987)
68. T.Hershcovici , K.Elishkevitz , R.Rotstein , R.Fusman , D.Zeltser , I. Shapira , N.Arber , D.Avitzour , S.Berliner , and Y.Beigel ,“The erythrocyte adhesiveness/aggregation test to rveal real-time information of rheological relevance in patients with familial and primary hypercholesterolemia beforeand following plasma exchange”, Therapeuic Apheresis , 6(2) , 140-144 (2001)
69. C.Otto , H.C.Geiss , M.G.Donner , K.G.Parhofer , and P.Schwandt , “Influence of atorvastatin versus simvastatin on fibrinogen and other hemorheological parameters in patients with severe hypercholesterolemia treated with regular low-density lipoprotein immunoadsorption apheresis”, Therapeutic Apheresis , 4(3) , 244-248 (1999)
70. M.Walzl ,“A promising approach to the treatment of
multi-infarct dementia”, Neruobiology of Aging , 21 , 283-287 (2000)
71. J.M.Rifkind , O.O.Abugo , R.R.Pewddada , N.Patel , D.Speer , C.
Balagopalakrishna , D.Danon , D.K.Ingram and E.L.Spangler ,
“Maze learning impairment is associated with stress hemopoiesis induced by chronic treatment of aged rats with human reconbinat”, Life Sciences , 64 , 237-247 (1999)
72. A.Maeda , M.Yamada , Y.Itoh , E.Otomo , M.Hayakawa and T.Miyatake , “Computer-assisted three-dimensional Image analysis of cerebral amyloid angiopathy”, Stroke , 24 , 1857-1864 (1993)
73. S.Usami , R.G.King , S.Chien , R.Skalak , C.R.Huang and
A.L.Copley ,“Microcinephotgraphic studies on red cell aggregation in
steady and oscillatory shear-anote”, Biorheology , 12 , 323-325(1975)
74. A.R.Koudinov , T.T.Berezov , and N.V.Koudinova , Commentary“Alzheimer’s amyloid beta and lipid metabolism：a missing link?”, Official Publication of the Federation of American Societies for Experimental Biology , Vol.12 (1998)
75. E.Fukadaand and M.Kaibara ,“ Viscoelastic study of aggregation of red blood cells ”, Biorheology , 17 , 177-182 (1979)
76. S.J. Rensburg , M.E.Carstens , F.C.V. Potocnik , A.K.Aucamp , J.J.F. Taljaard , and K.R.Koch , “ Membrane fluidity of platelets and erythrocytes in patients with Alzheimer’s disease and the effect of small amounts of aluminium of platelet and erythrocyte membranes”, Neurochemical Research , 17 , 825-829 (1992)
77. T.Rankinen , E.Hietanen , S.Väisänen , M.Lehtiö , I.Penttilä , C. Bouchard and R.Rauramaa , “ Relationship between lipid peroxidation and plasma fibrinogen in middle-aged men“ , Thrombosis Research , 99 , 453-459 (2000)
78. I.Bourdel-Marchasson , M.C.Delmas-Beauvieux , E.Peuchant , S. Richard-Harston , A.Decamps , B.Reignier , J.P. Emeriau and M. Rainfray , “ Antioxidant defences and oxidative stress markers in erythrocytes and plasma from normally nourished elderly Alzheimer patients ”, Age and Ageing , 30 , 235-241 (2001)
79. N.Morandas , M.R.Clark , M.S.Lacobs and S.B.Shohet , “ Analysis of factors regulating erythrocyte deformability ”, Journal of Clinical Investigation , 65 , 2416-2156 (1995)
80. M.A.Pappolla , R.A.Omar , K.S.Kim , and N.K.Robakis ,
“ Immunohistochemical evidence of antioxidant stress in Alzheimer’s Disease”, American Journal of Pathology , 140 , 621-628 (1992)
81. C.E.Teunissen , J.Vente , H.W. M.Steinbusch and C.Bruijn ,
“ Biochemical markers related to Alzheimer’s dementia in serum and cerebrospinal fluid ”, Neurobiology of Aging , 23 , 485-508 (2002)
82. G. Schramm：A Practical Approach to Rheology and Rheometry. International Standard Book Number Ch.3 , 1998.
83. K.Hensley , N.Hall , R.Subramaniam , P.Cole , M.Harris , M. Aksenov , M.Aksenova , S.P.Gabbita , J.F.Wu , J.M.Carney , M. Lovell , W.R.Markesbery , and D.A.Butterfield ,“ Brain regional correspondence between Alzheimer’s Disease histopathology and biomarkers of protein oxidation ”, Journal of Neurochemistry , 65 , 2416-2156 (1995)
84. D.L.Marcus , C.Thomas , C.Rodriguez , K.Simberkoff , J.S.Tsai , J.A. Strafaci , and M.L.Freedman ,“ Increased peroxidation and reduced antioxidant enzyme activity in Alzheimer’s disease ”, Experimental Neurology , 150 , 40-44 (1998)
85. E.Terzi , G.Hölzemann , and J.Sellig ,“Interaction of Alzheimerβ-amyloid pepitde(1-40) with lipid membranes ”, Biochemistry , 36 , 14845-14852 (1997)
86. R.Skalak ,“ Aggregation and disaggration of red blood cells ”, Biorheology , 21 , 463-476 (1984)
87. G. Heuser ,“Seconddary effects in cone and plate viscometers ”, Biorheology , 15 , 311-320 (1978)
88. T.-W.Chung , J.J.H. Yu and D.-Z.Liu ,“Reducing lipid peroxidation stress of erythrocyte membrane byα-Tocophero lNicotinate plays an important role in improving blood rheological properties in Type2 diabetic patients with retinopathy”, Journal of the British Diabetic Association , 15 , 80-385 (1998)
89. G.G.Glenner and C.W.Wong , “Alzheimer’s disease : Initial report of the purification and characterization of an ovel cerebrovascular amyloid protein”, Biochemical and Biophysical Research Communications , 120 , 885-890 (1984)
90. C.L.Masters , ”Amyloid plaque core protein in Alzheimer’s disease and Down syndrome”, Proceedings of the National Academy of Sciences , 82 , 4245—4249 (1985)
91. J.Kang , ”The precusor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor ”, Nature , 325 , 733-736 (1987)
92. C.Sestier , D.Sabolovic , D.Geldwerth , J.Roger , J.Pons and A. Halbreich , “ Use of annexin V ferro fluid to enumerate erythrocytes damaged in various pathologies or during storage in vitro ”, Comptes Rendus de L''Academie des Sciences. Serie III, 318 , 1141-1146 (1995)
93.D.E.Brooks, J.W.Goodwin and G.V.F.Seaman , ”Rheology of erythrocyte suspension : electrostatic factors in the dextranmediated aggregation of erythrocytes ”, Biorheology , 11 ,69-75 (1974)