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11.
胆固醇代谢与阿尔茨海默病关系的研究进展 总被引:1,自引:0,他引:1
在阿尔茨海默病(AD)发病机制中,占主导地位是Aβ瀑流学说:由于淀粉样前体蛋白的代谢紊乱,产生了过量的Aβ42,后者迅速聚集形成寡聚物,启动了Aβ瀑流效应,造成了Aβ的沉积,形成老年斑.越来越多的实验表明,胆固醇在Aβ的产生和异常沉积过程具有重要调节作用,同时Aβ对胆固醇调节也有反馈作用,探讨两者的相互作用和影响有助于AD发病机制的阐明.而与胆固醇代谢密切相关的因素,如载脂蛋白E、调节胆固醇代谢的药物等也成为研究的热点. 相似文献
12.
目的:探讨载脂蛋白A1、B基因多态性对非刨伤性股骨头坏死(avascular necrosis of the femoral head,ANFH)发生的影响.方法:应用聚合酶链反应对中国北方汉族143例ANFH患者和92例正常人分别扩增含Apo AI基因启动子-75 bp和第一内舍子 83 bp及Apo B基因Eco RI、XbaI和3-VNTR的DNA片段,限制性内切酶酶切扩增产物,琼脂糖凝胶电泳分离基因多态性.结果:Apo A1基因启动子-75 bp处,ANFH患者中A/A基因型频率明显高于正常组(P<0.01),而G/A基因型频率明显低于正常组(P<0.01).Apo AI内舍子 83 bp位点,Apo B基因Eco RI、Xba I位点和3-VNTR区域ANFH患者组和正常组基因型及等位基因频率分布无统计学差异.结论:Apo A1基因启动子区域-75bp位点A/A型可能是非创伤性股骨头坏死易感基因之一,但未能发现Apo A1第一内舍子 83 bp位点及Apo B基因Eco RI、XbaI和3-VNTR位点多态性与非创伤性股骨头坏死发生有明显的关系. 相似文献
13.
H. Förstl H. Sattel M. Sarochan C. Besthom C. Czech S. Daniel C. Geiger-Kabisch F. Hentschel R. Zerfass K. Beyreuther 《Der Nervenarzt》1996,67(9):730-738
Zusammenfassung
30 Patienten mit klinisch diagnostizierter Alzheimer-Demenz (AD) und 55 etwa gleichaltrige Kontrollprobanden wurden über einen
2-Jahres-Zeitraum prospektiv klinisch, neuroradiologisch und elektroenzephalographisch untersucht, um die longitudinalen Ver?nderungen
auf diesen Untersuchungsebenen und ihre Zusammenh?nge zu studieren. In der Kontrollgruppe waren im Beobachtungszeitraum keine
wesentlichen Ver?nderungen auf einer der Untersuchungsebenen zu verzeichnen. Bereits inital bestanden signifikante Unterschiede
zwischen Patienten und Kontrollen hinsichtlich der kognitiven Leistung, der Ventrikelweite und der absoluten Theta- und Delta-Power.
Innerhalb der Patientengruppe verschlechterten sich w?hrend des zweij?hrigen Beobachtungszeitraums die Werte der Blessed-Demenzskala
um 7 ± 7 Punkte und im Mini-Mental-State Test um 8 ± 4 Punkte. Die Volumina der Seitenventrikel weiteten sich um mehr als
30 % des Ausgangswertes und die absolute Delta- oder Theta-Power stieg um mehr als 10 % des Ausgangswertes an. Hierdurch nahmen
die Unterschiede zwischen Kontroll- und Patientengruppe nochmals zu. Wir konnten keine Zusammenh?nge zwischen Krankheitsbeginn,
Alter, Apolipoprotein E4 Gendosis und Krankheitsverlauf belegen. Ein initial schlechter Wert der Patienten auf der Blessed-Skala
war mit st?rkeren morphologischen und EEG-Ver?nderungen im Verlauf korreliert, w?hrend initial hohe Theta-Power eine st?rkere
funktionelle und kognitive Verschlechterung innerhalb der Patientengruppe pr?dizierte.
相似文献
14.
P. M. Mattila T. Koskela M. Röyttä T. Lehtimäki T. A. Pirttilä E. Ilveskoski P. Karhunen J. O. Rinne 《Acta neuropathologica》1998,96(4):417-420
We determined the apolipoprotein E (apoE) genotype in clinically diagnosed and neuropathologically verified cases of Parkinson’s
disease (PD) (n = 45), with or without Alzheimer (AD)-type changes, and compared the apoE genotype with that in healthy age-matched controls
(n = 59). The PD cases were divided into two groups according to the CERAD criteria: “O + A”, with no or only uncertain histological
findings of AD, and “B + C” with histological findings suggestive or indicative of AD. DNA was isolated from frozen brain
samples, and the apoE genotypes were determined using polymerase chain reaction amplification and subsequent restriction analysis
by HhaI enzyme. The frequency of the apoɛ4 allele (29.4%) was significantly increased in the B + C group. The odds ratio for an
apoɛ4 allele in the B + C group was 2.5 as compared to controls (95% confidence interval, 1.2–5.2). In the 0 + A group, the
frequency of apoɛ4 allele (13.6%) was similar to that in controls (14.4%) and the risk of an apoɛ4 allele was not increased
(odds ratio 0.94). The PD cases with an apoɛ4 allele had a greater number of cortical (P = 0.02) but not nigral Lewy bodies than those without an apoɛ4 allele (P = 0.57). The results show that neuropathologically verified PD as such is not associated with increased apoɛ4 allele frequency.
Received: 15 January 1998 / Revised, accepted: 24 March 1998 相似文献
15.
Stessman J Maaravi Y Hammerman-Rozenberg R Cohen A Nemanov L Gritsenko I Gruberman N Ebstein RP 《Mechanisms of ageing and development》2005,126(2):333-339
In an exploratory study, 11 common polymorphisms were examined for contributing to longevity including: apolipoprotein E (apoE), methylenetetrahydrofolate reductase (MTHFR), cathepsin D (CAD), superoxide dismutase 2 (SOD2), angiotensinogen (AGT) and insulin-like growth factor 2 (IGF2), Leiden factor 7, p53 oncogene, dopamine D4 receptor (DRD4) and the serotonin transporter (SERT). Genotype and allele frequencies of these genes were compared in 224 older (75 years) Jewish Jerusalem residents of Ashkenazi ethnicity to a group of 441 younger subjects (22 years). Nominally significant results provide suggestive evidence in the Ashkenazi group that apoE, MHTFR, SOD2, IGF2 ApaI, and factor VII are risk factors for a single outcome, survival to 75. Overall, the more genetically homogenous Ashkenazi ethnic group showed evidence for association in five genes examined suggesting that future studies in this population would gainfully focus on this ethnic group. 相似文献
16.
中国汉族人群APOE等位基因频率的初步研究 总被引:21,自引:2,他引:21
载脂蛋白E(apolipoproteinE,APOE)基因是一个多功能基因,除调节脂类及脂蛋白代谢之外,近年来还发现它与Alzheimer病及Ⅲ型高血脂症等病之间有密切关系。为对上述疾病进行病因学研究,作者采用一步法PCR技术对438名无亲缘关系的中国汉族健康受试者的APOE基因进行分型,并计算其基因频率分布,结果表明,中国治疗人群APOE3种等位基因的频率分别为:E2=0.0400,E3=0.8 相似文献
17.
Research into Alzheimer’s disease (AD) has been guided by the view that deposits of fibrillar amyloid-β peptide (Aβ) are neurotoxic and are largely responsible for the neurodegeneration that accompanies the disease. This ‘amyloid hypothesis’ has claimed support from a wide range of molecular, genetic and animal studies. We critically review these observations and highlight inconsistencies between the predictions of the amyloid hypothesis and the published data. We show that the data provide equal support for a ‘bioflocculant hypothesis’, which posits that Aβ is normally produced to bind neurotoxic solutes (such as metal ions), while the precipitation of Aβ into plaques may be an efficient means of presenting these toxins to phagocytes. We conclude that if the deposition of Aβ represents a physiological response to injury then therapeutic treatments aimed at reducing the availability of Aβ may hasten the disease process and associated cognitive decline in AD. 相似文献
18.
Shigemura K Shirakawa T Okada H Tanaka K Kamidono S Arakawa S Gotoh A 《Clinical and experimental medicine》2005,4(4):196-201
Abstract Familial hypercholesterolaemia is a genetic disorder characterised by high low-density lipoprotein (LDL) cholesterol concentrations,
which frequently gives rise to premature coronary artery disease (CAD). The clinical expression of familial hypercholesterolaemia
is highly variable even in patients carrying the same LDL receptor gene mutation. This variability may be due to environmental
and other genetic factors. Apolipoprotein E (Apo-E) has been extensively studied for its effects on the phenotype of familial
hypercholesterolaemia. In this study we examined the influence of Apo-E genotype on lipid parameters and the incidence of
CAD in 93 Greek patients with familial hypercholesterolaemia. Apo-E E2, E3 and E4 allele frequencies were 0.06, 0.86 and 0.09
respectively. The levels of total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apolipoproteins A and B and
lipoprotein α did not differ significantly among carriers and non-carriers of the E4 allele. The prevalence of CAD and hypertension
did not differ either. Our results suggest that the E4 allele is not associated with lipid levels or with the prevalence of
CAD among familial hypercholesterolaemia patients of the Greek population.
*The two authors were equally involved in the work 相似文献
19.
G. Feussner M. Eichinger R. Ziegler 《Journal of molecular medicine (Berlin, Germany)》1992,70(11):1027-1035
Summary Nineteen adult patients with type III hyperlipoproteinemia (HLP) and homozygosity for apolipoprotein (apo) E2 were treated with the 3-hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase inhibitor simvastatin (20 or 40 mg per day) alone or in combination with the fibrate derivative gemfibrozil (450 mg per day) during a 30-week outpatient study. With the 20-mg dose (n = 19) the mean plasma cholesterol level decreased from 13.24±8.04 8.04 at baseline to 8.04±4.19 mmol/l (mean reduction 39.3%; P<0.05), and the mean plasma triglyceride level decreased from 13.47±19.22 to 7.84±7.71 mmol/l (–41.8%; NS); this was due to a decrease in very low density lipoprotein (VLDL) cholesterol from 8.95±8.64 to 4.94±4.24mmo1/l (–44.8%; NS), a decrease in low density lipoprotein (LDL) cholesterol from 3.54±0.93to 2.25 ± 0.59 mmol/l (–36.5%; P<0.01), and an increase in high density lipoprotein (HDL) cholesterol from 0.72±0.28 to 0.85±0.34 (+18.1%; NS). Thirteen patients were treated with 40 mg simvastatin per day. Under this regimen there was a further significant decrease in LDL cholesterol from 2.33±0.62 to 1.81±0.49 mmol/l (–22.3%; P<0.01). In six patients who remained hyperlipidemic on monotherapy combination drug therapy with simvastatin (40 mg per day) and gemfibrozil (450 mg per day) was given. Compared to simvastatin alone the addition of gemfibrozil further lowered plasma concentrations of total cholesterol by 14.9%, VLDL cholesterol by 23.5%, and triglycerides by 17.1%, although this was not statistically significant. No patient was discontinued from single or combination drug therapy, and no severe clinical or biochemical side effects were observed. The results of this study demonstrate the usefulness of simvastatin in the therapy of type III HLP and indicate that in individual patients who remain hyperlipidemic on monotherapy combination drug therapy with both of these drugs is effective in further reducing plasma concentrations of total cholesterol, VLDL cholesterol, and triglycerides. Although no patient in this investigation developed myopathy or rhabdomyolysis, combined fibrate-HMG CoA reductase inhibitor treatment should be considered only for severe forms of hyperlipidemia and for patients who do not respond sufficiently to mon-therapy of any of these drugs.Abbreviations Apo
Apolipoprotein
- CPK
creatine phosphokinase
- GGT
gamma-glutamyl transpeptidase
- HDL
high density lipoproteins
- HLP
hyperlipoproteinemia
- HMG CoA
3-hydroxy-3-methyl glutaryl coenzyme A
- IDL
intermediate density lipoproteins
- LDL
low density lipoproteins
- TG
triglycerides
- VLDL
very low density lipoproteins 相似文献
20.
Takada D Emi M Ezura Y Nobe Y Kawamura K Iino Y Katayama Y Xin Y Wu LL Larringa-Shum S Stephenson SH Hunt SC Hopkins PN 《Journal of human genetics》2002,47(12):0656-0664