A5016196614- Alzheimer's disease research and treatments
- Metabolomics and Mass Spectrometry Studies
- Mass Spectrometry Techniques and Applications
- Computational Drug Discovery Methods
- Prion Diseases and Protein Misfolding
- Advanced Proteomics Techniques and Applications
- Sphingolipid Metabolism and Signaling
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Lung Cancer Research Studies
- Brain Metastases and Treatment
- Protein Structure and Dynamics
- Enzyme Structure and Function
- Nuclear Receptors and Signaling
- Analytical Chemistry and Chromatography
- Bioinformatics and Genomic Networks
- Cancer Immunotherapy and Biomarkers
- Neuroinflammation and Neurodegeneration Mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Nerve injury and regeneration
- Neurogenesis and neuroplasticity mechanisms
- Cholesterol and Lipid Metabolism
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Neuroendocrine Tumor Research Advances
- Histone Deacetylase Inhibitors Research
University of Gothenburg
2016-2025
Uppsala University
2024-2025
Science for Life Laboratory
2024-2025
University College London
2020-2024
Stanford University
2021-2023
Sahlgrenska University Hospital
2019-2022
National Hospital for Neurology and Neurosurgery
2022
UK Dementia Research Institute
2022
Multimodal chemical imaging using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) can provide comprehensive molecular information in situ within the same tissue sections. This is of relevance for studying different brain pathologies such as Alzheimer's disease (AD), where recent data suggest a critical colocalizing Aβ peptides and neuronal lipids. We here developed novel trimodal, high-resolution (10 μm) MALDI MS (IMS) paradigm negative positive ion mode lipid...
Lipid dysregulations have been critically implicated in Alzheimer's disease (AD) pathology. Chemical analysis of amyloid-β (Aβ) plaque pathology transgenic AD mouse models has demonstrated alterations the microenvironment direct proximity Aβ In studies, differences lipid patterns linked to structural polymorphism among pathology, such as diffuse, immature, and mature fibrillary aggregates, also reported. To date, no comprehensive neuronal changes human tissue performed. Here, for first time,...
The major pathological hallmarks of Alzheimer's disease (AD) are the progressive aggregation and accumulation beta-amyloid (Aβ) hyperphosphorylated tau protein into neurotoxic deposits. Aβ has been suggested as critical early inducer, driving progression. However, factors that promote remain elusive. Imaging mass spectrometry (IMS) is a powerful technique to comprehensively elucidate spatial distribution patterns lipids, peptides, proteins in biological tissue sections. In present study,...
Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) enables acquisition of spatial distribution maps for molecular species in situ. This can provide comprehensive insights on the pathophysiology different diseases. However, current sample preparation and MALDI-IMS methods have limitations preserving histological tissue morphology, resulting interfered correspondence data with subsequently acquired immunofluorescent staining results. We here investigated...
Abstract Lithium (Li) is a potent mood stabilizer and displays neuroprotective neurogenic properties. Despite extensive investigations, the mechanisms of action have not been fully elucidated, especially in juvenile, developing brain. Here we characterized lithium distribution juvenile mouse brain during 28 days continuous treatment that result clinically relevant serum concentrations. By using Time-of-Flight Secondary Ion Mass Spectrometry- (ToF-SIMS) based imaging were able to delineate...
The Uppsala APP deletion leads to Alzheimer’s disease by modulating α- and β-secretase cleavage of accelerating Aβ fibrillization.
Amyloid plaque formation constitutes one of the main pathological hallmarks Alzheimer's disease (AD) and is suggested to be a critical factor driving pathogenesis. Interestingly, in patients that display amyloid pathology but remain cognitively normal, Aβ deposits are predominantly diffuse morphology suggesting cored primarily associated with cognitive deterioration AD Little known about molecular mechanism responsible for conversion monomeric into neurotoxic aggregates observed AD. The...
The pathological mechanisms underlying Alzheimer's disease (AD) are still not understood. pathology is characterized by the accumulation and aggregation of amyloid-β (Aβ) peptides into extracellular plaques, however factors that promote neurotoxic Aβ remain elusive. Imaging mass spectrometry (IMS) a powerful technique to comprehensively elucidate spatial distribution patterns lipids, proteins in biological tissues. In present study, matrix-assisted laser desorption/ionization (MALDI)...
Metabolic isotope labeling and imaging mass spectrometry delineate early events of precipitating Aβ plaque pathology.
Abstract Understanding of Alzheimer's disease (AD) pathophysiology requires molecular assessment how key pathological factors, specifically amyloid β (Aβ) plaques, influence the surrounding microenvironment. Here, neuronal lipids have been implicated in Aβ plaque pathology, though lipid microenvironment direct proximity to plaques is still not fully resolved. A further challenge microenvironmental heterogeneity, across structurally polymorphic features, such as diffuse, immature, and mature,...
Alzheimer's disease (AD) is a neurodegenerative disorder that develops over decades. Glial cells, including astrocytes are tightly connected to the AD pathogenesis, but their impact on progression still unclear. Our previous data show take up large amounts of aggregated amyloid-beta (Aβ) unable successfully degrade material, which instead stored intracellularly. The aim present study was analyze astrocytic Aβ deposits composition in detail order understand role propagation. For this purpose,...
We present a novel, correlative chemical imaging strategy based on multimodal matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MSI), hyperspectral microscopy, and spatial chemometrics. Our workflow overcomes challenges associated with MSI data acquisition alignment by implementing 1 + 1-evolutionary image registration for precise geometric of their integration in common, truly matrix maintained resolution (10 μm). This enabled multivariate statistical modeling using...
ABSTRACT Amyloid plaque deposition is recognized as the primary pathological hallmark of Alzheimer’s disease(AD) that precedes other events and cognitive symptoms. Plaque pathology represents itself with an immense polymorphic variety comprising plaques different stages amyloid fibrillization ranging from diffuse to fibrillar, mature plaques. The association Aβ AD pathogenesis, clinical symptoms disease progression remains unclear. Advanced chemical imaging tools, such functional microscopy...
Abstract Lipid droplets (LDs) are crucial for energy homeostasis, but also involved in a wide spectrum of other cellular processes. Accumulating data identifies LDs as an important player inflammation. However, the underlying mechanisms and impact on neuroinflammation remain unclear. Here, we describe novel function human astrocytes, context Alzheimer’s disease (AD). Although, overall lipid profile was unchanged astrocytes with AD pathology, our show clear effect LD metabolism specific fatty...
Abstract Amyloid-beta (Aβ) plaque formation in Alzheimer’s disease (AD) pathology is morphologically diverse. Understanding the association of polymorphic Aβ with AD pathogenesis and progression critical light emerging Aβ-targeting therapies. In this work, functional amyloid microscopy enhanced by deep learning was integrated mass spectrometry imaging to delineate plaques identify their associated make-up. both sporadic ( n = 12) familial 6), dense-core showed higher levels Aβ1-40 N-terminal...
MALDI mass spectrometry imaging (MSI) enables label-free, spatially resolved analysis of a wide range analytes in tissue sections. Quantitative MSI datasets is typically performed on single pixels or manually assigned regions interest (ROIs). However, many sparse, small objects such as Alzheimer's disease (AD) brain deposits amyloid peptides called plaques are neither nor ROIs. Here, we propose new approach to facilitate the comparative computational evaluation plaque-like by MSI: fast...
One of the major hallmarks Alzheimer's disease (AD) pathology is formation extracellular amyloid β (Aβ) plaques. While Aβ has been suggested to be critical in inducing and, potentially, driving disease, molecular basis AD pathogenesis still under debate. Extracellular plaque manifests itself upon aggregation distinct peptides, resulting morphologically different morphotypes, including mainly diffuse and cored senile As precipitates long before any clinical symptoms occur, targeting processes...
Imaging mass spectrometry (IMS) is a promising new chemical imaging modality that generates large body of complex data, which in turn can be approached using multivariate analysis approaches for image and segmentation. Processing IMS raw data critically important proper interpretation has significant effects on the outcome analysis, particular statistical modeling. Commonly, processing methods are chosen based rational motivations rather than comparative metrics, though no quantitative...