Sirkka Goebeler

Apolipoprotein E―Dependent Accumulation of Alzheimer Disease―Related Lesions Begins in Middle Age

To study the prevalence and age dependency of senile plaques (SP) and neurofibrillary tangles (NFT), the brain changes characteristic of Alzheimer disease (AD), and their association with apolipoprotein E (APOE) genotypes in a community‐dwelling normal population.

Indoors forensic entomology: Colonization of human remains in closed environments by specific species of sarcosaprophagous flies

Fly species that are commonly recovered on human corpses concealed in houses or other dwellings are often dependent on human created environments and might have special features in their biology that allow them to colonize indoor cadavers. In this study we describe nine typical cases involving forensically relevant flies on human remains found indoors in southern Finland. Eggs, larvae and puparia were reared to adult stage and determined to species. Of the five species found the most common were Lucilia sericata Meigen, Calliphora vicina Robineau-Desvoidy and Protophormia terraenovae Robineau-Desvoidy. The flesh fly Sarcophaga caerulescens Zetterstedt is reported for the first time to colonize human cadavers inside houses and a COI gene sequence based DNA barcode is provided for it to help facilitate identification in the future. Fly biology, colonization speed and the significance of indoors forensic entomological evidence are discussed.

Identification of different bacterial DNAs in human coronary arteries

Background  Various studies have suggested a link between infection, atherosclerosis and coronary artery disease. We studied whether bacterial DNA is present in coronary specimens obtained from left anterior descending coronary arteries of subjects having sudden deaths of cardiovascular and other causes, as verified by an autopsy.

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Gene Is a Risk Factor of Large-Vessel Atherosclerosis Stroke

Background/Purpose Genetic variation in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene has been recently identified as an important determinant of plasma LDL-cholesterol and severity of coronary heart disease. We studied whether the PCSK9 gene is linked to the risk of ischemic stroke (IS) and with the development of intracranial atherosclerosis. Methods/Results The pivotal E670G polymorphism, tagging an important haplotype of the PCSK9 gene, was genotyped in two independent studies. The Belgium Stroke Study included 237 middle aged (45–60) Belgian patients, with small-vessel occlusion (SVO) and large-vessel atherosclerosis stroke (LVA), and 326 gender and ethnicity matched controls (>60 yrs) without a history of stroke. In multivariate analysis the minor allele (G) carriers appeared as a significant predictor of LVA (OR = 3.52, 95% CI 1.25–9.85; p = 0.017). In a Finnish crossectional population based consecutive autopsy series of 604 males and females (mean age 62.5 years), G-allele carriers tended to have more severe allele copy number-dependent (p = 0.095) atherosclerosis in the circle of Willis and in its branches. Conclusion Our findings in this unique combination of clinical and autopsy data, provide evidence that PCSK9 gene associates with the risk of LVA stroke subtype, and suggest that the risk is mediated by the severity of intracranial atherosclerosis.

Apolipoprotein E genotype is related to plasma levels of C-reactive protein and lipids and to longevity in nonagenarians.

Objective  Apolipoprotein E (APOE) genotype is a regulator of hepatic lipoprotein metabolisms and has been linked with longevity. The relationship between APOE genotype and plasma C‐reactive protein (CRP), which is produced by the liver during inflammation, has not been studied in nonagenarians. The aim of the present study was to establish whether APOE genotype is related to plasma concentrations of CRP and lipids, or longevity among nonagenarians.

Medical history, cognitive status and mobility at the age of 90. A population-based study in Tampere, Finland

Background and aims: The oldest-old population is expanding rapidly. There is a new need for clinical information about this group, which is actively using social and health care. We studied the population of people born in 1907–1910 and living in the city of Tampere (Finland) at the age 90 (N=916, 79.4% women, 20.6% men); 71.7% of the population lived in the community and 28.3% in institutions. Methods: Medical records of 832 (90.8%) nonagenarians were obtained. We registered diagnoses of chronic diseases or diseases that required hospitalization at any time of their lives, as well as physicians’ notes on their memory and mobility. Diseases were coded and grouped according to ICD-10. Results: The most common diagnosis groups were cardiovascular diseases (78.3%), gastrointestinal diseases (58.6%), infections (53.6%) and trauma (49.6%). There was an average of 8 chronic or severe diseases mentioned in patient records. The diagnosis of dementia was mentioned in 26.7% of cases, most of them living in institutions; a problem with memory — from for-getfulness to dementia — was mentioned in 35.9% of cases; 37.5% were able to move using no or a light support, 8.3% were bedridden. Conclusions: We conclude that this age group suffers from numerous chronic diseases influencing mobility and cognition. Dementia seems to be the most important symptom leading to institutionalization.

Coronary artery calcification is related to functional polymorphism of matrix metalloproteinase 3: the Helsinki Sudden Death Study

Matrix metalloproteinase 3 (MMP3) is expressed in human coronary atherosclerotic lesions and is known to be involved in degradation of the plaque and to be co-localized with calcium and fibrin deposits in advanced lesions, indicating a possible role of MMP3 in arterial calcification. The MMP3 gene promoter polymorphism leads to low promoter activity 6A6A, intermediate promoter activity 5A6A and high promoter activity 5A5A genotypes. To determine whether these genotypes predict the extent of atherosclerosis we investigated their association with different types of coronary lesions in an autopsy series of 300 middle-aged white Finnish men (aged 35-69 years) from the Helsinki Sudden Death Study (HSDS). Areas of the coronary wall covered with different atherosclerotic lesions were measured and MMP3 genotypes were determined by PCR and minisequencing. In men >/=53 years the mean area of calcified lesion in the most severely affected coronary artery was significantly associated with the MMP3 genotype (P=0.029). Subjects with high promoter activity genotypes had on average larger calcified lesion areas than those with the low-activity genotype. The MMP3 genotype (P=0.025) persisted as an independent predictor of mean calcified lesion area after stepwise adjustment for age, BMI, hypertension, diabetes, number of affected vessels and smoking. These data provide evidence that the proposed effect of MMP3 in the process of atherogenesis may be modified by the MMP3 genotype.

Association of the endothelial nitric oxide synthase gene polymorphism with risk of coronary artery disease and myocardial infarction in middle-aged men.

Abstract. Nitric oxide (NO), formed by endothelial constitutive nitric oxide synthase (eNOS) maintains endothelium-dependent vasodilatation and also mediates antithrombotic actions. The eNOS gene harbours a common polymorphism in intron 4 (4a/b), and some clinical studies have suggested an association of the rare a-allele with coronary artery disease (CAD) and myocardial infarction (MI). However, contradictory results have also been reported. We studied associations of eNOS polymorphism with CAD and MI in two prospective autopsy series comprising altogether 700 Caucasian Finnish men, who died suddenly. In ANCOVA, no significant differences in areas of atherosclerotic lesions and coronary stenosis percentages were found between men carrying the a-allele (ba+aa) compared with those homozygous for the b-allele. Subjects with the a-allele had significantly lower risk of MI (odds ratio 0.44, 95% confidence interval 0.25–0.77, P=0.004) compared with those carrying the bb genotype. Men with the a-allele also tended to have coronary thrombosis less often (odds ratio 0.43, 95% confidence interval 0.18–1.01, P=0.055). The eNOS gene 4a/b polymorphism was not associated with the extent of coronary atherosclerosis, but the a-allele of the variant seems to protect to some degree against the development of MI.

Large Vessel Cerebral Atherosclerosis Is Not in Direct Association with Neuropathological Lesions of Alzheimer’s Disease

Introduction: Cerebral hypoperfusion caused by large vessel atherosclerosis has been suggested to be associated with the pathogenesis of sporadic Alzheimer’s disease (AD). Atherosclerosis and AD share risk factors such as age, diabetes, hypercholesterolemia, hypertension and apolipoprotein E ε4 (APOE ε4) allele. We studied the association between atherosclerosis of the circle of Willis (CW) and AD neuropathology in a large autopsy sample. Methods: The present study comprised a consecutive autopsy series (n = 466) representing noninstitutionalized general population aged 50 years and over (mean 70.8, SD 11.5 years). The atherosclerosis of CW was scored semiquantitatively and the amyloid plaque (AP) load in the frontal cortex and the number of neurofibrillary tangles (NFT) in the hippocampus were measured. Results: In a linear regression model, AP percentage area was associated with age (p < 0.0001) and APOE ε4 allele (p < 0.0001), but not with CW score (p = 0.70) or gender (p = 0.11). Similarly, the NFT count was predicted only by age (p > 0.0001), and not by CW score (p = 0.36), gender (p = 0.41) or APOE ε4 allele (p = 0.072). Conclusion: Our results suggest that cerebral large vessel atherosclerosis is not in direct association with APs or NFTs – hallmarks of AD neuropathology.

Radiographic Assessment of Dental Health in Middle-aged Men Following Sudden Cardiac Death

Poor oral health has been suggested to be a risk factor for myocardial infarction. To study if dental pathology might predispose to pre-hospital sudden cardiac death, and using a sum index of panoramic tomography findings, we compared the oral health of middle-aged (33–69 yrs) male victims (Helsinki Sudden Death Study) of sudden cardiac death (n = 117) with that of controls, who died of non-cardiac diseases (n = 63) or suffered unnatural sudden death (n = 120). The mean number of teeth was 15.2, and 17.4% of the men were edentulous. Frequent age-associated findings in dentate victims were fillings (79.9%), horizontal bone loss (72.1%), periapical lesions (45.6%), residual roots (38.2%), and vertical pockets (30.9%). In multivariate analysis with coronary heart disease risk factors and number of teeth as covariates, poor oral health was associated (p = 0.053) with the risk of sudden cardiac death along with age, smoking, and body mass index. This association was especially strong (p = 0.009) among victims < 50 yrs.