| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Apolipoprotein A-IV and transportation of cholesterol from smooth muscle cells in experimental hyperlipidemia Wang, Z., M. She, et al. (1995), Zhonghua Bing Li Xue Za Zhi 24(1): 8-10. Abstract: The effects of apolipoprotein (apo) A-IV and apoA-IV/phosphatidylcholine (PC) liposome on cholesterol efflux from the smooth muscle cells originating from the aorta of hypercholesterolemic rabbit model and control rabbits, and on the activation of lecithin cholesterol acyltransferase (LCAT) were studied respectively. Both apoA-IV/PC and apoA-I/PC liposomes have similar efficiency as the HDL's, i.e. a strong ability to clear intracellular cholesterol and the ability to activate LCAT. There were no differences noticed on the clearance ability between apoA-IV and apoA-I or between apoA-IV/PC and apoA-I/PC liposomes. These results suggest that apoA-IV may play an important role in the process of reverse cholesterol transport and apoA-IV/PC liposome may be effectively used instead of natural HDL to prevent the development of atherosclerosis. |
| Apolipoprotein B (apo B) signal peptide length polymorphisms are associated with apo B, low density lipoprotein cholesterol, and glucose levels in Mexican Americans Kammerer, C. M., J. L. VandeBerg, et al. (1996), Atherosclerosis 120(1-2): 37-45. Abstract: We investigated the effects of apolipoprotein (apo) B signal peptide length polymorphisms on low density lipoprotein cholesterol (LDL-C), apo B, and post-challenge (2 h) glucose levels in 686 Mexican Americans from 34 families. The most common allele encoded an apo B signal peptide of 27 amino acids (ins; SP-27), the next most frequent allele encoded a 24 amino acid signal peptide (del; SP-24), and the rarest allele encoded a 29 amino acid signal peptide (ins; SP-29) that has been found only in Mexican Americans. Homozygotes for the SP-24 allele had significantly higher mean levels of apo B. LDL-C, and 2-h glucose than SP-27 homozygotes, and SP-27/SP-24 heterozygotes had intermediate levels (P = 0.01 for apo B, P < 0.001 for LDL-C, and P = 0.04 for 2-h glucose). Heterozygotes for the SP-29 allele had higher apo B and LDL-C levels compared to homozygotes for the SP-27 or SP-24 alleles. Apo B signal peptide length polymorphism accounted for 4.2%, 3.5%, and 3.0% of the residual variation in LDL-C, apo B, and 2-h glucose levels, respectively, among the Mexican American families. |
| Apolipoprotein B and A-I in relation to serum cholesterol and triglycerides in 43,000 Swedish males and females Jungner, I., G. Walldius, et al. (1992), Int J Clin Lab Res 21(3): 247-55. Abstract: Automated methods for the determination of apolipoprotein B and apolipoprotein A-I were developed, tested, and applied in screening programs of large populations to improve information about the composition and degree of hyperlipoproteinemia. Apolipoproteins B and A-I, total cholesterol, and triglyceride levels were measured in 25,659 males and 18,144 females between 20 and 79 years of age, the majority subjectively healthy. The immunoturbidimetric methods used for apolipoproteins B and A-I were shown to be stable over time, and the errors of the methods were below 7%. Apolipoprotein B correlated with total cholesterol (r = 0.86, P less than 0.001) for each age decile group and for both sexes (r = 0.82-0.87, P less than 0.001). For a subsample comparable to the large population, apolipoprotein B correlated with cholesterol in low density (i.e., the atherogenic particle), r = 0.89, P less than 0.001. The mean values for apolipoprotein B increased with age for both sexes, with much higher levels in males than in females under 50 years of age. Apolipoprotein A-I was lower in males than in females in all age-groups. At all cholesterol levels males had higher apolipoprotein B, and at the same triglyceride level, also lower apolipoprotein A-I and hence a higher B/A-I ratio than females. Using apolipoprotein B and A-I (high-density lipoprotein cholesterol) particles and adopting Swedish consensus criteria for the diagnosis of risk of ischemic heart disease, examples are given showing that many individuals, especially females, with high or borderline total serum cholesterol can be excluded from further investigation/treatment for hypercholesterolemia.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Apolipoprotein B and LDL cholesterol: which parameter(s) should be included in the assessment of cardiovascular risk? Bloch, S. and R. Couderc (1998), Ann Biol Clin (Paris) 56(5): 539-44. Abstract: High level of plasma apo B lipoproteins is a risk factor for coronary artery disease. However, which lipid parameters should be routinely assayed is a question still in debate. For this purpose, the authors have studied issues since 1992 comparing predictive and discriminative values of LDL-cholesterol and apo B in order to assess coronary artery disease. Indeed the respective advantages of these markers were still being discussed after an exhaustive review had been completed in 1992. Despite the number of the debates, none of the few studies about this topic rise any decisive arguments. In conclusion it is proposed that a true comparison of the predictive values of LDL-cholesterol and apo B should be carried out before making definitive recommendations concerning their clinical utility. |
| Apolipoprotein B gene DNA polymorphisms (EcoRI and MspI) and serum lipid levels in the Serbian healthy population: interaction of rare alleles and smoking and cholesterol levels Glisic, S., I. Savic, et al. (1995), Genet Epidemiol 12(5): 499-508. Abstract: The frequency of restriction fragment length polymorphisms (RFLPs) of the apolipoprotein B (apo B) gene, detected by EcoRI and MspI, and their influence on serum lipids were studied in a total of 239 healthy subjects from the Belgrade area. The influence of interaction between different genotypes and smoking was also studied. The relative frequency of both rare R2 and M2 alleles (lacking the cutting site) was similar to that reported in other groups of Caucasians (0.16 and 0.11, respectively). No association was observed between the apo B genotypes and serum lipid levels adjusted for age, body mass index, and blood pressure either in the whole sample or in either women or men. When smokers and non-smokers were considered separately, smoking had a significant impact on total cholesterol variability in all individuals with genotype M1M2 and high density lipoprotein (HDL) cholesterol variability in women with genotype R1R2. The presence of the rare alleles of these two polymorphisms in smokers was associated with lower lipid levels in the whole sample and in both women and men analyzed separately, except for an increase of HDL cholesterol level in male smokers, heterozygous for EcoRI polymorphism (R1R2). |
| Apolipoprotein B gene mutations affecting cholesterol levels Farese, R. V., Jr., M. F. Linton, et al. (1992), J Intern Med 231(6): 643-52. Abstract: In the past 5 years, many different mutations in the apolipoprotein (apo) B gene have been described that affect plasma cholesterol levels. More than 20 different mutations in the apoB gene have been shown to cause familial hypobetalipoproteinaemia, a condition characterized by abnormally low plasma concentrations of apoB and LDL cholesterol. Almost all of the mutations are nonsense or frameshift mutations that interfere with the translation of a full-length apoB100 molecule. Many, but not all, of these apoB gene mutations result in the synthesis of a truncated species of apoB that can be detected within the plasma lipoproteins. Familial hypobetalipoproteinaemia heterozygotes are almost always asymptomatic and have LDL cholesterol levels about one-quarter to one-third of those of unaffected family members. Several homozygotes and compound heterozygotes for familial hypobetalipoproteinaemia have been described. In these individuals, the LDL cholesterol levels are extremely low, usually less than 5 or 10 mg dl-1, and the clinical phenotype is variable, ranging from completely asymptomatic to severe problems related to intestinal fat malabsorption. One missense mutation in the apoB gene (an Arg----Gln substitution at apoB amino acid 3500) is associated with very poor binding of apoB100 to the cellular LDL receptor. This syndrome has been designated familial defective apolipoprotein B (FDB). The amino-acid substitution at residue 3500 delays the clearance of LDL from the plasma and results in hypercholesterolaemia. In some Western populations, the frequency of FDB heterozygotes appears to be as high as 1 in 500 individuals. |
| Apolipoprotein B in cholesterol-containing drusen and basal deposits of human eyes with age-related maculopathy Malek, G., C. M. Li, et al. (2003), Am J Pathol 162(2): 413-25. Abstract: Lipids accumulate in Bruch's membrane (BrM), a specialized vascular intima of the eye, and in extracellular lesions associated with aging and age-related maculopathy (ARM). We tested the hypothesis that ARM and atherosclerotic cardiovascular disease share molecules and mechanisms pertaining to extracellular lipid accumulation by localizing cholesterol and apolipoprotein B (apo B) in BrM, basal deposits, and drusen. Human donor eyes were preserved <4 hours postmortem and cryosectioned. Sections were stained with traditional lipid stains and filipin for esterified and unesterified cholesterol or probed with antibodies to apo B, apo E, and apo C-III. Normal adult retinal pigment epithelium (RPE) was subjected to RT-PCR and Western blot analysis for apolipoprotein mRNA and protein. Esterified and unesterified cholesterol was present in all drusen and basal deposits of ARM and normal eyes. Both apo B and apo E but not apo C-III were found in BrM, drusen, and basal deposits. Fewer macular drusen were stained by traditional lipid stains and apolipoprotein antibodies than peripheral drusen. RPE contained apo B and apo E mRNA and protein. Finding cholesterol and apo B in sub-RPE deposits links ARM with important molecules and mechanisms in atherosclerosis initiation and progression. The combination of apo B mRNA and protein in RPE raises the possibility that intraocular assembly of apo B-containing lipoproteins is a pathway involved in forming cholesterol-enriched lesions in ARM. |
| Apolipoprotein B signal peptide polymorphism and plasma LDL-cholesterol response to low-calorie diet Jemaa, R., A. Mebazaa, et al. (2004), Int J Obes Relat Metab Disord 28(7): 902-5. Abstract: OBJECTIVE: To assess the effect of the apolipoprotein B Ins/Del signal peptide. Polymorphism on plasma lipid levels in overweight subjects before and after a low-calorie diet. DESIGN: Diet intervention study (25% reduction in energy intake during 2.5 months) in relation to genetic factors. SUBJECTS: A total of 231 unrelated patients (146 women/85 men) recruited on the basis of body mass index (BMI)> or =25 kg/m(2). MEASUREMENTS: BMI, waist to hip ratio, blood lipids and lipoproteins, at entry and after 2.5 months, determination of apo B Ins/Del genotypes. RESULTS: On spontaneous diet, subjects carrying the Del allele had higher LDL-cholesterol (Del/Del: 3.97+/-0.62 mmol/l; Ins/Del: 3.87+/-1.01 mmol/l; Ins/Ins: 3.61+/-0.88 mmol/l) (P=0.038). When submitted to low-calorie diet, subjects with Del/Del genotypes reduced their LDL-cholesterol (-16.8%) more than subjects with Ins/Del or Ins/Ins (-4.7% and +0.9%, respectively) (P=0.001). CONCLUSION: In overweight or obese people, the response of plasma LDL-cholesterol levels to low-calorie diet is modulated by genetic variation at the apo B locus. Overweight subjects with the Del allele of the apo B signal peptide polymorphism are predisposed to high LDL cholesterol levels but their LDL cholesterol responds well to diet. These results demonstrate the importance of the interaction between genes and nutritional environment in the determination of the lipid levels. |
| Apolipoprotein B, fibrinogen, HDL cholesterol, and apolipoprotein(a) phenotypes predict coronary artery disease in hemodialysis patients Koch, M., B. Kutkuhn, et al. (1997), J Am Soc Nephrol 8(12): 1889-98. Abstract: Patients with end-stage renal disease have a markedly elevated risk for coronary artery disease (CAD). Lipids and most lipoproteins, however, seem to be not predictive for CAD in these patients. Although there is clear evidence that lipoprotein(a) Lp(a) is significantly elevated in these patients, no study with a sufficiently large group of hemodialysis patients has investigated the relationship between CAD and Lp(a), as well as the genetically determined apolipoprotein(a) apo(a) phenotype. This cross-sectional study determines the prevalence of CAD in relation to the cardiovascular risk profile in an unselected population of 607 hemodialysis patients, of which 33% were diabetic patients. Twenty-six percent (n = 158) of all patients suffered from CAD as diagnosed by a definitive myocardial infarction (n = 102) and/or at least one stenosis >50% of a coronary artery (n = 143). In univariate analysis, several classic risk factors, including the concentration of lipids, lipoproteins, apolipoproteins, and fibrinogen, correlated with CAD. Lp(a) in patients with CAD showed only a tendency to higher levels, without reaching significance, compared with patients without CAD (26.6 +/- 30.8 mg/dl versus 22.1 +/- 30.4 mg/dl, P = 0.10). The frequency of low molecular weight apo(a) isoforms, however, was significantly greater in the group with CAD (34.8% versus 23.6%, P < 0.01). Stepwise logistic regression analysis found seven variables associated with CAD: apolipoprotein B, the low molecular weight apo(a) phenotype, male sex, age, fibrinogen, diabetes mellitus, and HDL cholesterol. The association of these variables with CAD differed depending on age. These results indicate that, besides classic risk factors such as age, sex, and diabetes mellitus, additional factors of the lipoprotein and fibrinolytic system contribute to the high prevalence of CAD in hemodialysis patients. |
| Apolipoprotein B, ratio of total cholesterol to HDL-C, and blood pressure in abdominally obese white and black American women Okosun, I. S., S. Choi, et al. (2001), J Hum Hypertens 15(5): 299-305. Abstract: OBJECTIVE: To compare the association of apolipoprotein B (ApoB) and total cholesterol to high-density lipoprotein cholesterol (TC/HDL) with blood pressure in abdominally obese white and black American women. We also sought to determine if there are ethnic differences in blood pressure values that could be explained by differences in mean values of ApoB and TC/HDL. METHODS: Data (n = 1844) from the Third US National Health and Nutrition Examination Survey were used in this study. Abdominal obesity was defined as waist circumference (WC) of > or =88cm or having WC greater than what was expected as predicted from residuals obtained from linear regression of WC on BMI. Bi-variate Pearson's correlation analysis was used to quantify the degree of association of ApoB and TC/HDL with blood pressure and other lipids. Multiple linear regression analysis was used to assess the independent contribution of ApoB and TC/HDL to blood pressure, adjusting for age, total cholesterol, alcohol intake, and smoking. To determine ethnic differences in blood pressure values associated with ApoB or TC/HDL, dummy variables were used to compare blacks with whites fitted in multiple regression models, while adjusting for age, total cholesterol, alcohol intake and smoking. RESULTS: Elevated ApoB was positively associated with diastolic and systolic blood pressure (DBP/SBP) in blacks and whites, independent of age, total cholesterol, alcohol intake and smoking (P < 0.01). Elevated TC/HDL was also positively associated with increased DBP and SBP in whites (P < 0.05). For the same value of ApoB and TC/HDL whites had higher values of DBP and SBP than blacks, adjusting for confounding variables. CONCLUSIONS: Compared with TC/HDL, ApoB was more strongly associated with DBP and SBP in both abdominally obese white and black women. Since ApoB is associated with hypertension, the combination of elevated ApoB and hypertension may identify a group of patients with more marked risk of vascular disease, thus, warranting further investigation. |
| Apolipoprotein B-100 gene mutations and cholesterol control in German patients Loggen, U., A. Boden, et al. (2003), Atherosclerosis 166(2): 411-2. |
| Apolipoprotein B-100 gene Xba I polymorphism and cholesterol gallstone disease Han, T., Z. Jiang, et al. (2000), Clin Genet 57(4): 304-8. Abstract: The apolipoprotein (apo) B gene Xba I polymorphism is associated with alterations in serum lipids. Disturbances in serum lipids may be a risk factor for cholesterol gallstone disease. However, the relation between the Xba I polymorphism and cholesterol gallstones is unknown. This study was aimed at characterizing the polymorphism of the apo B gene Xba I in patients with gallbladder stones and the association of Xba I polymorphism with serum lipids. Xba I genotypes were measured by PCR-RFLP, and serum lipids assayed in 190 patients with gallbladder stones and 441 control subjects. The frequency of the X+/- genotype (20.63 vs. 7.94%) and X+ allele (10.79 vs. 3.97%) was significantly higher in the patient group than in the control group. Patients with the X+/- genotype had a significantly higher concentration of total cholesterol, low-density lipoprotein (LDL)-cholesterol, and apo B in serum than patients with the X-/- genotype. The X+ allele of the apo B gene is characterized by a higher cholesterol concentration and a higher LDL-cholesterol concentration in serum, and it may be a marker for increased risk of cholesterol gallstone disease. |
| Apolipoprotein composition and particle size affect HDL degradation by chymase: effect on cellular cholesterol efflux Lee, M., P. T. Kovanen, et al. (2003), J Lipid Res 44(3): 539-46. Abstract: Mast cell chymase, a chymotrypsin-like neutral protease, can proteolyze HDL3. Here we studied the ability of rat and human chymase to proteolyze discoidal pre beta-migrating reconstituted HDL particles (rHDLs) containing either apolipoprotein A-I (apoA-I) or apoA-II. Both chymases cleaved apoA-I in rHDL at identical sites, either at the N-terminus (Tyr18 or Phe33) or at the C-terminus (Phe225), so generating three major truncated polypeptides that remained bound to the rHDL. The cleavage sites were independent of the size of the rHDL particles, but small particles were more susceptible to degradation than bigger ones. Chymase-induced truncation of apoA-I yielded functionally compromised rHDL with reduced ability to promote cellular cholesterol efflux. In sharp contrast to apoA-I, apoA-II was resistant to degradation. However, when apoA-II was present in rHDL that also contained apoA-I, it was degraded by chymase. We conclude that chymase reduces the ability of apoA-I in discoidal rHDL particles to induce cholesterol efflux by cleaving off either its amino- or carboxy-terminal portion. This observation supports the concept that limited extracellular proteolysis of apoA-I is one pathophysiologic mechanism leading to the generation and maintenance of foam cells in atherosclerotic lesions. |
| Apolipoprotein E (ApoE) and ApoE-rich high-density cholesterol as potential early diagnostic markers of congenital biliary tract anomalies Nagasaka, H., H. Kikuta, et al. (2003), J Pediatr 143(3): 411. |
| Apolipoprotein E accelerates the efflux of cholesterol from macrophages: mechanism of xanthoma formation in apolipoprotein E deficiency Kinoshita, M., M. Kawamura, et al. (2000), J Atheroscler Thromb 6(1): 22-7. Abstract: A patient with congenitally deficient apolipoprotein (apo) E showed numerous tuberoerutive, tendon xanthomas and severe atherosclerosis, despite a low LDL concentration. In order to study the mechanism of xanthoma formation observed in apo E deficient patients, we evaluated the effect of VLDL and HDL from the patient on cholesterol ester (CE) accumulation in macrophages. The results showed that there was no difference in CE formation in macrophages among normal VLDL, the patient's VLDL and apo E containing VLDL, which was prepared by incubation of the patient's VLDL with recombinant apo E. On the other hand, apo E containing HDL, which was prepared by incubation of the patient's HDL with recombinant apo E, accelerated cholesterol efflux more effectively than did the patient's HDL and decreased intracellular CE content. Moreover, free apo E accelerated cholesterol efflux from lipid loaded macrophages. These results suggest that macrophages are prevented from transforming into foam cells by their secretion of apo E. This may also explain the marked atherosclerosis and xanthomatosis observed in the patient with apo E-deficiency. |
| Apolipoprotein E affects serial changes in total and low-density lipoprotein cholesterol in adolescent girls: Project HeartBeat! Fulton, J. E., S. Dai, et al. (1999), Metabolism 48(3): 285-90. Abstract: Apolipoprotein E (apo E) polymorphism is a genetic determinant of lipid and lipoprotein levels and the risk for coronary heart disease. The extent to which serial patterns of change in total cholesterol and low-density lipoprotein cholesterol (LDL-C) concentrations varied by apo E genotype was therefore investigated in 247 Caucasian girls aged 8 to 14 at baseline who were participating in Project HeartBeat! a mixed longitudinal study of cardiovascular disease (CVD) risk factor development in children. Plasma lipid concentrations were determined for each participant three times per year (every 4 months) for up to 4 years from October 1991 through August 1995. Mean total cholesterol values for individuals with epsilon2/3, epsilon3/3, and epsilon3/4 genotypes were 141.7, 161.6, and 165.9 mg/dL, respectively (P <.001). Corresponding LDL-C values for individuals with epsilon2/3, epsilon3/3, and epsilon3/4 genotypes were 74.6, 94.8, and 98.7 mg/dL, respectively (P <.001). The results of longitudinal modeling indicated that age trajectories for total cholesterol and LDL-C varied significantly by apo E genotype. Individuals with epsilon3/3 and epsilon3/4 genotypes exhibited similar patterns of change in total cholesterol and LDL-C from ages 8 to 18, while individuals with the epsilon2/3 genotype demonstrated a significantly different pattern of change (age2 x genotype interaction, P <.05). For example, individuals with the epsilon2/3 genotype showed a slight increase in total cholesterol from approximately 141 to 146 mg/dL from ages 8 to 10; total cholesterol then decreased monotonically from ages 10 to 18 from 146 to 115 mg/dL. The apo E effect on total cholesterol and LDL-C and their change during adolescence is strong and may be modified by factors affecting growth, maturation, and reproductive function. |
| Apolipoprotein E and activity of cholesterol esters transport in type IIA and IIB hyperlipoproteinemia Tvorogova, M. G., T. A. Rozhkova, et al. (1997), Ter Arkh 69(12): 30-3. Abstract: The authors studied the activity of cholesterol esters transport (CET), concentrations of apolipoprotein E in the blood and high density lipoproteins (HDLP) in parallel with other parameters of lipoprotein metabolism in 79 males and 62 females. 122 of them had ischemic heart disease (IHD) and primary hyperlipoproteinemia (HLP). 19 healthy controls were normolipidemic. Activation of CET and relative lowering of apoE content in HDLP with relevant increase in lipoproteins containing apoB were seen only in type IIB HLP. CET activity in controls was related to a significant positive correlation with concentrations of both cholesterol (CS) and CS esters (CSE) in HDLP and HDLP3 and negative correlation with the proportion free CS/CSE in HDLP. Opposite to normolipidemic subjects, in type IIB HLP there was a negative relationship between CET activity and HDLP3 CS level and positive--between free CS/CSE in HDLP but not with concentration of CSE and total CS in HDLP. In type IIA HLP patients no relationships were registered between CET activity and HDLP content of total CS and CSE as well as with HDLP3 CS level. In type IIB HLP a significant correlation was found between level of HDLP CS and CET activity. Concentration of apoE in HDLP correlated with apoB level in the serum but not with quantity of HDLP CS. Patients with type IIA HLP exhibited a significant negative correlation between CET activity and HDLP apoE. These patients had no dependence of CET activity on HDLP CS but had positive correlation between HDLP apoE and HDLP CS in the serum. Thus, defects of reverse CS transport may be induced not only by changes in CET activity but also by apoE distribution among lipoproteins of different classes. |
| Apolipoprotein E and cholesterol Miettinen, T. A. (1990), Duodecim 106(11): 857-60. |
| Apolipoprotein E and cholesterol affect neuronal calcium signalling: the possible relationship to beta-amyloid neurotoxicity Hartmann, H., A. Eckert, et al. (1994), Biochem Biophys Res Commun 200(3): 1185-92. Abstract: Besides the neurotoxic properties of beta-amyloid (beta A4), apolipoprotein E polymorphism seems to play an important role in the pathogenesis of sporadic Alzheimer's disease (AD). The calcium amplifying effect of beta A25-35 (the neurotoxic sequence of beta A4) in dissociated mouse brain neurons and human lymphocytes was nearly abolished by cholesterol (100-500 mumol/l). This effect may be related to the membrane stabilizing properties of cholesterol which could be confirmed by measurements of membrane fluidity. ApoE did not affect the Ca2+ amplifying effect of beta A25-35, but amplified the neuronal Ca2+ response significantly in a very low concentration (100nmol/l). The findings suggest a possible link between AD pathology and ApoE polymorphism by the calcium amplifying effect of ApoE itself as well as by the modulation of beta A4 neurotoxicity by cholesterol. |
| Apolipoprotein E and cholesterol metabolism in the pathogenesis and treatment of Alzheimer's disease Poirier, J. (2003), Trends Mol Med 9(3): 94-101. Abstract: There is much evidence suggesting that there is a strong relationship between the deterioration of brain lipid homeostasis, vascular changes and the pathogenesis of Alzheimer's disease (AD). These associations include: (1). recognition that a key cholesterol transporter, apolipoprotein E type 4, acts a major genetic risk factor for both familial and sporadic AD; (2). epidemiological studies linking cardiovascular risk factors, such as hypertension and high plasma cholesterol, to dementia; (3). the discovery that small strokes can precipitate clinical dementia in cognitively normal elderly subjects; (4). the modulation of degradation of the amyloid precursor protein by cholesterol administration in cell culture and in animal models of beta-amyloid overproduction; and (5). the beneficial effect of cholesterol-lowering drugs, such as Probucol and statins, in combating common AD. The recent finding that there is a genetic association between the HMGR gene locus and sporadic AD further suggests that brain cholesterol metabolism is central to AD pathophysiology, and a potential therapeutic target for disease stabilization and primary disease prevention. |