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Amyloid fibrils of α-synuclein (α-syn) are a component of Lewy bodies, the characteristic hallmark of Parkinson's disease. Amyloid fibrils arise through primary nucleation from monomers, which in the case of α-syn is often heterogeneous, followed by the growth of the nuclei by monomer addition. Secondary nucleation corresponds to the formation of new fibrils facilitated by pre-existing fibrils. Wh

Red cell distribution width (RDW) has been suggested to have a predictive potential for several cardiovascular diseases, but its association with abdominal aortic aneurysm (AAA) is unknown. We examined whether RDW is associated with the risk of AAA among 27,260 individuals from the population-based Malmö Diet and Cancer Study cohort. Data of baseline characteristics were collected during 1991–1996

Research into Alzheimer's disease is still hampered by a lack of fundamental understanding of the underlying mechanisms. While the aggregation of the amyloid β peptide (Aβ) into amyloid fibrils is highly implicated as a key factor in the disease, the molecular nature of its involvement has proven complex and elusive. This thesis and the work herein is part of an ongoing effort to map out the aggre

Oligomeric species populated during the aggregation of the Aβ42 peptide have been identified as potent cytotoxins linked to Alzheimer’s disease, but the fundamental molecular pathways that control their dynamics have yet to be elucidated. By developing a general approach that combines theory, experiment and simulation, we reveal, in molecular detail, the mechanisms of Aβ42 oligomer dynamics during

Aims/hypothesis: Non-Western immigrants to Europe are at high risk for type 2 diabetes. In this nationwide study including incident cases of type 2 diabetes, the aim was to compare all-cause mortality (ACM) and cause-specific mortality (CSM) rates in first- and second-generation immigrants with native Swedes. Methods: People living in Sweden diagnosed with new-onset pharmacologically treated type

In addition to their fundamental role in clearance, the kidneys release select molecules into the circulation, but whether any of these anabolic functions provides insight on kidney health is unknown. Using aptamer-based proteomics, we characterized arterial (A)-to-renal venous (V) gradients for >1,300 proteins in 22 individuals who underwent invasive sampling. Although most of the proteins that c

Background: Most literature on second primary cancers (SPCs) focuses on possible factors, which may increase the risk of these cancers, and little attention has been paid for the overall incidence differences between first primary cancers (FPCs) and same SPCs. We wanted to compare the incidence rates for all common cancers when these were diagnosed as FPCs and SPCs after invasive and in situ squam

Crystals, nanoparticles, and fibrils catalyze the generation of new aggregates on their surface from the same type of monomeric building blocks as the parent assemblies. This secondary nucleation process can be many orders of magnitude faster than primary nucleation. In the case of amyloid fibrils associated with Alzheimer's disease, this process leads to the multiplication and propagation of aggr

Background: Traumatic brain injury (TBI) is a major cause of disabilities and mortality worldwide, with higher prevalence in offender populations than in the general population. Previous research has strongly advocated increased awareness of TBI in offender populations. The aim of this study was to explore the prevalence and characteristics of TBI, and to investigate associations and interactions

Background: Long-term exposure to air pollution increases the risk of cardiovascular morbidity and mortality, but the mechanisms are not fully known. Current evidence suggests that air pollution exposure contributes to the development of atherosclerosis. There are few studies investigating associations between air pollution and carotid plaques, a well-known precursor of cardiovascular disease. Met

Chest pain is one of the most common complaints at the emergency department (ED), and it is commonly the perceived likelihood of acute coronary syndrome (ACS) that drives management. Guidelines from the European Society of Cardiology (ESC) recommend the use of a 0-/1-h high-sensitivity cardiac troponin T (hs-cTnT) protocol to rule out or in ACS, but this is mostly based on observational studies. T

Chronic kidney disease (CKD) is a multifactorial disorder with an important genetic component, and several studies have demonstrated potential associations with allelic variants. In addition, CKD patients are also characterized by high levels of genomic damage. Nevertheless, no studies have established relationships between DNA damage, or genomic instability present in CKD patients, and gene polym

Background: Parkinson's disease (PD) is a neurodegenerative disease with an often complex component identifiable by genome-wide association studies. The most recent large-scale PD genome-wide association studies have identified more than 90 independent risk variants for PD risk and progression across more than 80 genomic regions. One major challenge in current genomics is the identification of the

Membrane proteins perform a vast range of vital biological functions and are the gatekeepers for exchange of information and matter between the intracellular and extracellular environment. However, membrane protein interactions can be challenging to characterise in a quantitative manner due to the low solubility and large size of the membrane protein complex with associated lipid or detergent mole

Investigations of social-genetic effects, whereby a social partner’s genotype affects another’s outcomes, can be confounded by the influence of the social partner’s rearing environment. We used marital information on more than 300,000 couples from Swedish national data to disentangle social-genetic from rearing-environment effects for alcohol use disorder (AUD). Using observational and extended-fa

BACKGROUND: Infantile malignant osteopetrosis (IMO) is an autosomal recessive disorder characterized by non-functional osteoclasts and a fatal outcome early in childhood. About 50% of patients have mutations in the TCIRG1 gene. METHODS: IMO iPSCs were generated from a patient carrying a homozygous c.11279G>A (IVS18+1) mutation in TCIRG1 and transduced with a lentiviral vector expressing human TCIR

Background: Epidemiological associations between maternal concentrations of perfluoroalkyl substances (PFAS) and birth weight are inconsistent. There is concern that studies based on samples collected in late pregnancy may be confounded by kidney function but studies of the relation between pregnancy-induced changes in PFAS and kidney function are lacking. Our aims were to investigate changes in s

Purpose: The influence of allograft ischemic time (IT) on short- and long-term mortality remains under debate in lung transplantation (LTx). Due to a scarcity in donors, better understanding of IT might improve the outcome after LTx. Methods: Between January 1990 and June 2016; 307 patients underwent LTx at Lund university hospital, Sweden. The end-point used was death/Re-LTx assessed by Cox regre

Difficulty in obtaining bone tissue is an obstacle to studying epigenetics to understand gene–environment interactions, and their role in disease pathogenesis. Blood is an obvious alternative and in this proof of principle study, our aim was to systematically investigate whether blood is a viable surrogate for bone. We measured epigenome-wide DNA methylation at 850 K CpG sites in matched trabecula