Eighty-three brains obtained at autopsy from nondemented and demented individuals were examined for extracellular amyloid deposits and intraneuronal neurofibrillary changes. The distribution pattern and packing density of amyloid deposits turned out to be of limited significance for differentiation of neuropathological stages. Neurofibrillary changes occurred in the form of neuritic plaques, neurofibrillary tangles and neuropil threads. The distribution of neuritic plaques varied widely not only within architectonic units but also from one individual to another. Neurofibrillary tangles and neuropil threads, in contrast, exhibited a characteristic distribution pattern permitting the differentiation of six stages. The first two stages were characterized by an either mild or severe alteration of the transentorhinal layer Pre-alpha (transentorhinal stages I-II). The two forms of limbic stages (stages III-IV) were marked by a conspicuous affection of layer Pre-alpha in both transentorhinal region and proper entorhinal cortex. In addition, there was mild involvement of the first Ammon's horn sector. The hallmark of the two isocortical stages (stages V-VI) was the destruction of virtually all isocortical association areas. The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations.

Neuropathological stageing of Alzheimer-related changes.

Detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III)

So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to

Human biochemical genetics

Inherited genetic variation has a critical but as yet largely uncharacterized role in human disease. Here we report a public database of common variation in the human genome: more than one million single nucleotide polymorphisms (SNPs) for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted. These data document the generality of recombination hotspots, a block-like structure of linkage disequilibrium and low haplotype diversity, leading to substantial correlations of SNPs with many of their neighbours. We show how the HapMap resource can guide the design and analysis of genetic association studies, shed light on structural variation and recombination, and identify loci that may have been subject to natural selection during human evolution.

/pdf/a-haplotype-map-of-the-human-genome-2oc85odzud.pdf

A haplotype map of the human genome

2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular riskThe Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS)

Amplification of the hypervariable region close to the apolipoprotein B gene: application to forensic problems.

The roles of HDL and plasma triglyceride concentrations as risk factors for coronary heart disease have attracted increasing attention. One protein, apolipoprotein A-IV (apoA-IV), is involved in the metabolism of both triglycerides and HDL. ApoA-IV has been linked with the hydrolysis of triglyceride-rich lipoproteins and with the interconversion of HDL subfractions. ApoA-IV has also been suggested to participate in several stages of reverse cholesterol transport. Structural and functional alterations of apolipoproteins, caused by a variety of mutations, have been shown to influence lipoprotein metabolism in several ways. Uncertainty about the exact biochemical function of apoA-IV has made the use of genetic apoA-IV variants attractive in evaluating its physiological role.

Molecular biology of apolipoprotein A-iv

The influence of apolipoprotein (apo) E polymorphism on the association between body fatness and concentrations of serum lipoprotein variables was studied in a random subsample (n = 892) of 8- to 17-year-old children from a total community. Covariates (age, race, and sex)-adjusted mean values of percent body fat, ponderal index (wt/ht3), and subscapular skinfold thickness differed significantly among apo E phenotype groups, with the apo E2 group (n = 61) carrying E2/2 and E3/2 phenotypes having significantly (P < .01) lower values than the apo E3 group (n = 480) carrying the E3/3d phenotype. In the apo E3 group, covariates-adjusted partial correlation coefficients showed significant (P < .05 to P < .001) associations between obesity measures and lipoprotein variables studied that are generally seen in populations. However, these associations, with the exception of low-density lipoprotein (LDL) cholesterol and apo B, were altered in the other apo E phenotype groups. In the apo E2 group, obesity measures correlated significantly with triglycerides (P < .05 to P < .001), but not with very-low-density lipoprotein (VLDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and apo A-I. In contrast, in the apo E4 group (n = 212) carrying E4/3 and E4/4 phenotypes, obesity measures correlated significantly with HDL cholesterol (P < .05 to P < .001) and apo A-I (P < .01), but not with triglycerides and VLDL cholesterol. Therefore, the apo E phenotype should be taken into account in the association between body fatness and serum lipoproteins.

Relationship between obesity and serum lipoproteins in children with different apolipoprotein E phenotypes: the Bogalusa Heart Study.

BACKGROUND An increasing volume of evidence suggests that haemostatic factors play a role in the risk of coronary heart disease. It is not known, however, whether between-population differences in haemostatic factors correspond with the differences in mortality related to coronary heart disease. We examined this question in Finland, where, in North Karelia (in the eastern part of the country), the mortality from coronary heart disease is 1.5-1.7 times higher than that in southwestern areas. METHODS A random sample of 3000 people aged 45-64 years was drawn from the population registers of North Karelia, of the area surrounding Turku and Loimaa in southwestern Finland and of the Helsinki area in southern Finland. Of the 3000 people approached, 79.6% took part in the study. differences in coronary heart disease mortality and morbidity. RESULTS Factor-VII coagulant activity was significantly higher in North Karelia than in the other areas (P = 0.0008). The fibrinogen level was also higher in North Karelia, although the difference was significant only among non-smokers (P = 0.02). Levels of factor-VII antigen, plasminogen and lipoprotein (a) did not differ between the areas. Within North Karelia, the levels of both factor-VII coagulant activity, and factor-VII antigen were higher in rural areas than in urban areas. Levels of factor-VII coagulant activity, factor-VII antigen and plasminogen were higher in women than in men and increased with age in women but not in men. The fibrinogen level increased with age in both sexes. CONCLUSION These baseline findings of the Finrisk Haemostasis Study demonstrate that the geographical differences in levels of factor-VII coagulant activity and fibrinogen in Finland are consistent with the population

Christian Ehnholm

Papers

Amplification of the hypervariable region close to the apolipoprotein B gene: application to forensic problems.

Molecular biology of apolipoprotein A-iv

Relationship between obesity and serum lipoproteins in children with different apolipoprotein E phenotypes: the Bogalusa Heart Study.

Haemostatic factors and lipoprotein (a) in three geographical areas in Finland: the Finrisk Haemostasis Study.

Altered hepatic lipid status and apolipoprotein A-I metabolism in mice lacking phospholipid transfer protein