Cerebrospinal fluid-induced retardation of amyloid ß aggregation correlates with Alzheimer's disease and the APOE ε4 allele.

Misfolding and aggregation of amyloid ß (Aß) are key features of Alzheimer's disease (AD) pathogenesis, but the molecular events controlling this process are not known in detail. In vivo, Aß aggregation and plaque formation occur in the interstitial fluid of the brain extracellular matrix. This fluid communicates freely with cerebrospinal fluid (CSF). Here, we examined the effect of human CSF on Aß aggregation kinetics in relation to AD diagnosis and carrier status of the apolipoprotein E (APOE) ε4 allele, the main genetic risk factor for sporadic AD. The aggregation of Aß was inhibited in the presence of CSF and, surprisingly, the effect was more pronounced in APOE ε4 carriers. However, by fractionation of CSF using size exclusion chromatography, it became evident that it was not the ApoE protein itself that conveyed the inhibition, since the retarding species eluted at lower volume, corresponding to a much higher molecular weight, than ApoE monomers. Cholesterol quantification and immunoblotting identified high-density lipoprotein particles in the retarding fractions, indicating that such particles may be responsible for the inhibition. These results add information to the yet unresolved puzzle on how the risk factor of APOE ε4 functions in AD pathogenesis.

Free triiodothyronine is associated with smoking habit, independently of obesity, body fat distribution, insulin, and metabolic parameters.

BACKGROUND: The aim of this study was to examine the relationship between thyroid hormones and smoking and several other parameters like age, gender, insulin, and anthropometric and metabolic parameters in subjects with a wide range of body mass index (BMI). PATIENTS AND METHODS: A total of 931 euthyroid normal weight (BMI<25.0 kg/m2), overweight and obese subjects (BMI ≥25.0 kg/m2), 663 women and 268 men, aged 18-68 yr, were investigated. Fasting TSH, free T3 (FT3), free T4 (FT4), insulin, glucose, and lipid serum levels were determined. Waist circumference was measured as an indirect parameter of central fat accumulation. RESULTS: Smokers were younger (p<0.001) and showed higher FT3 (p<0.01), and triglyceride (p<0.01) levels and lower glucose (p<0.01) and HDL (p<0.001) concentrations than non smoking subjects. FT3 levels were directly associated with BMI (p<0.001), waist circumference (p<0.001), insulin (p<0.001), and triglyceride (p<0.01) levels and negatively correlated with age (p<0.001) and HDL-cholesterol levels (p<0.001). When a multiple regression analysis was performed with FT3 levels as the dependent variable, and smoking, age, gender, and TSH, insulin, triglyceride, and HDL-cholesterol serum concentrations as independent variables, FT3 levels maintained an independent positive association with smoking (p<0.05), age (p<0.001), male sex (p<0.001), waist circumference (p<0.05), and insulin levels (p<0.001). CONCLUSIONS: Smoking increases FT3 levels independently of age, gender, obesity, body fat distribution and metabolic parameters.

Lipid profile in a tertiary care center.

INTRODUCTION: Lipid profile is changing with changing developmental status and lifestyle in less developed countries and coronary artery disease risk factor is rising. The aim of the study is to find the lipid pattern in Department of Medicine in tertiary care hospital. METHODS: An observational prospective study was conducted in 408 subjects from January 2009 to February 2010. Study subjects were selected irrespective of co-morbid condition and coronary risk factors. RESULTS: The mean triglycerides, cholesterol, LDL, HDL were 138.3 +/- 78.3 mg/dl, 180.2 +/- 53.7 mg/dl, 113.8 +/- 41.2 mg/dl, 40.1 +/- 10.1 mg/dl respectively. The Triglycerides (>140 mg/dl), Cholesterol (>250 mg/dl), LDL (>92 mg/dl), HDL (<45mg/dl) were 35.5%, 7.6%, 67.9%, 76% respectively. CONCLUSIONS: Lipid profile is becoming atherogenic with high triglyceride, high LDL and low HDL being the most common abnormality. An epidemiological study is recommended to understand the true burden of the disease in the community.

Neurodegenerative disorders and cholesterol.

It has been suggested that a high serum cholesterol level is a risk factor for Alzheimer's disease (AD), that treatment with cholesterol-lowering drugs (statins) reduces the frequency of AD development, and that the polymorpholism of genes encoding proteins regulating cholesterol metabolism is associated with the frequency of AD development. However, the mechanism by which high serum cholesterol level leads to AD, still remains unclarified. Several recent studies have shown the results challenging the above notions. Here another notion is proposed, that is, a low high-density lipoprotein (HDL) level in serum and cerebro-spinal fluid (CSF) is a risk factor for the development of AD; moreover, the possibility that AD and Niemann-Pick type C disease share a common cascade, by which altered cholesterol metabolism leads to neurodegeneration (tauopathy) is discussed. In this review, the association between cholesterol and AD pathogenesis is discussed from different viewpoints and several basic issues are delineated and addressed to fully understand the mechanisms underlying this relationship.