A5070084115- Alzheimer's disease research and treatments
- Cholesterol and Lipid Metabolism
- Receptor Mechanisms and Signaling
- Cholinesterase and Neurodegenerative Diseases
- Hormonal Regulation and Hypertension
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Parkinson's Disease Mechanisms and Treatments
- Redox biology and oxidative stress
- Computational Drug Discovery Methods
- Cellular transport and secretion
- Autophagy in Disease and Therapy
- Dementia and Cognitive Impairment Research
- Nuclear Receptors and Signaling
- Mitochondrial Function and Pathology
- Estrogen and related hormone effects
- Tryptophan and brain disorders
- S100 Proteins and Annexins
- Diet and metabolism studies
- Endoplasmic Reticulum Stress and Disease
- Peroxisome Proliferator-Activated Receptors
- Metabolomics and Mass Spectrometry Studies
- Neuropeptides and Animal Physiology
- Retinoids in leukemia and cellular processes
- Neurogenesis and neuroplasticity mechanisms
Karolinska Institutet
2015-2024
Sanofi (France)
2019-2023
Immune Therapy Holdings (Sweden)
2020-2021
Alzheimer’s Disease Neuroimaging Initiative
2014
Karolinska University Hospital
2005-2009
Mutations in DJ-1, PINK1 (PTEN-induced putative kinase 1) and parkin all cause recessive parkinsonism humans, but the relationships between these genes are not clearly defined. One event associated with loss of any is altered mitochondrial function. Recent evidence suggests that turnover damaged mitochondria by autophagy might be central to process parkinsonism. Here, we show DJ-1 leads polarization, fragmentation accumulation markers (LC3 punctae lipidation) around human dopaminergic cells....
The risk of dementia and Alzheimer's disease (AD) probably results from an interaction between genetic environmental factors. aim this study was to investigate the effects putative interactions apoE epsilon4 allele lifestyle related factors for AD. Participants Cardiovascular Risk Factors, Aging, Dementia (CAIDE) were derived random, population-based samples previously studied in 1972, 1977, 1982 or 1987. After average follow-up 21 years, 1449 individuals (72.5%) aged 65-79 years re-examined...
PTEN-induced novel kinase 1 (PINK1) mutations are associated with autosomal recessive parkinsonism. Previous studies have shown that PINK1 influences both mitochondrial function and morphology although it is not clearly established which of these primary events secondary. Here, we describe a mechanism linking dysfunction alterations in related to PINK1. Cell lines were generated by stably transducing human dopaminergic M17 cells lentiviral constructs increased or knocked down As previous...
Alzheimer's disease (AD) is the most prevalent form of dementia with an estimated worldwide prevalence over 30 million people, and its incidence expected to increase dramatically increasing elderly population. Up until now, cerebrospinal fluid (CSF) has been preferred sample investigate central nervous system (CNS) disorders since composition directly related metabolite production in brain. In this work, a nontargeted metabolomic approach based on capillary electrophoresis–mass spectrometry...
Abstract Introduction Our objective was to compare the levels of three synaptic proteins involved in different steps transmission: Rab3A, SNAP25, and neurogranin, common forms dementia: Alzheimer's disease (AD), dementia with Lewy bodies (DLB), Parkinson's dementia. Methods A total 129 postmortem human brain samples were analyzed regional specific manner exploring their associations morphologic changes cognitive decline. Results We have observed robust reflecting dysfunction all studied...
Levels of the cyclic nucleotides guanosine 3', 5'-monophosphate (cGMP) or adenosine (cAMP) that play important roles in memory processes are not characterized Alzheimer's disease (AD). The aim this study was to analyse levels these cerebrospinal fluid (CSF) samples from patients diagnosed with clinical and prodromal stages AD expression level enzymes hydrolyzed them [phosphodiesterases (PDEs)] brain vs.For cGMP cAMP CSF analysis, cohort (n = 79) included cognitively normal participants...
Evidence is accumulating that the main chronic diseases of aging Alzheimer's disease (AD) and type-2 diabetes mellitus (T2DM) share common pathophysiological mechanisms. This study aimed at applying systems biology approaches to increase knowledge shared molecular pathways underpinnings AD T2DM. We analysed transcriptomic data post-mortem T2DM human brains obtain signatures combined them with protein-protein interaction information construct two disease-specific networks. The overlapping...
The brain-specific enzyme CYP46A1 controls cholesterol turnover by converting into 24 S -hydroxycholesterol (24OH). Dysregulation of brain and reduced levels are observed in Alzheimer’s disease (AD). In this study, we report that overexpression aged female mice leads to enhanced estrogen signaling the hippocampus improved cognitive functions. contrast, age-matched overexpressing males show anxiety-like behavior, worsened memory, elevated 5α-dihydrotestosterone hippocampus. We that, neurons,...
Abstract INTRODUCTION Polypharmacy is common among older adults and people with dementia. Multi‐medication therapy poses risks of harm but also targets comorbidities risk factors associated dementia, offering therapeutic potential. METHODS We evaluated the effects two polypharmacy regimens monotherapies on male female App NL‐G‐F knock‐in mice. assessed functional, emotional, cognitive outcomes;amyloid pathology; serum metabolomics profiles. RESULTS A combination metoprolol, simvastatin,...
In spite of the fact that cholesterol does not pass blood-brain barrier, hypercholesterolemia has been linked to increase Alzheimer's disease (AD) risk. Hypertension is another risk factor and angiotensin converting enzyme (ACE) activity known be increased in AD. Furthermore, a lower incidence AD reported patients taking anti-hypertensive drugs. Here we show levels angiotensinogen (AGT) ACE are cerebrospinal fluid (CSF) with mild cognitive impairment Moreover, CSF positively correlated both...
Insulin signalling deficiencies and insulin resistance have been directly linked to the progression of neurodegenerative disorders like Alzheimer's disease. However, date little is known about underlying molecular mechanisms or state distribution in brain under pathological conditions. Here, we report that accumulated retained as oligomers hyperphosphorylated tau-bearing neurons disease several most prevalent human tauopathies. The intraneuronal accumulation dependent on tau...
Background.Low vitamin D status is associated with poorer cognitive function in older adults, but little known about the potential impact on cerebrospinal fluid (CSF) biomarkers and brain volumes. The objective of this study was to examine relations between plasma 25-hydroxyvitamin (25(OH)D) impairment, CSF Alzheimer's disease (AD), structural tissue
Hypercholesterolemia is associated with cognitively deteriorated states. Here, we show that excess 27-hydroxycholesterol (27-OH), a cholesterol metabolite passing from the circulation into brain, reduced in vivo brain glucose uptake, GLUT4 expression, and spatial memory. Furthermore, patients exhibiting higher 27-OH levels had 18F-fluorodeoxyglucose uptake. This interplay between uptake revealed engagement of insulin-regulated aminopeptidase (IRAP). increased activity IRAP, countered IRAP...
Abstract Given sex‐related differences in brain disorders, it is of interest to study if there a sex difference the permeability blood‐cerebrospinal fluid barrier ( BCSFB ) and blood‐brain BBB ). The CSF /serum albumin ratio Q A lb standardized biomarker that evaluates function these barriers. In previous studies, contradictory results have been reported with respect using this quotient, possibly because small population sizes heterogeneity ages. measurements more than 20 000 patients...