A5040612602- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Neuroscience and Neuropharmacology Research
- Cholesterol and Lipid Metabolism
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Glycosylation and Glycoproteins Research
- Medicinal Plants and Neuroprotection
- Parkinson's Disease Mechanisms and Treatments
- Cholinesterase and Neurodegenerative Diseases
- Functional Brain Connectivity Studies
- Memory and Neural Mechanisms
- Advanced Neuroimaging Techniques and Applications
- Nuclear Receptors and Signaling
- Calpain Protease Function and Regulation
- Fatty Acid Research and Health
- Nerve injury and regeneration
- Neurological Disease Mechanisms and Treatments
- Connective tissue disorders research
- Liver Disease Diagnosis and Treatment
- Diet and metabolism studies
- Metabolomics and Mass Spectrometry Studies
- Ubiquitin and proteasome pathways
- Supramolecular Self-Assembly in Materials
- 14-3-3 protein interactions
- Wnt/β-catenin signaling in development and cancer
University of Gothenburg
2018-2024
Sahlgrenska University Hospital
2020-2022
Karolinska Institutet
2014
Istituto di Fisiologia Clinica
1994
Abstract Blood phosphorylated tau (p-tau) biomarkers, including p-tau217, show high associations with Alzheimer’s disease (AD) neuropathologic change and clinical stage. Certain plasma p-tau217 assays recognize forms additionally at threonine-212, but the contribution of p-tau212 alone to AD is unknown. We developed a blood-based immunoassay that specific without cross-reactivity p-tau217. Here, we examined diagnostic utility p-tau212. In five cohorts ( n = 388 participants), showed...
Abstract Abnormal accumulation of misfolded and hyperphosphorylated tau protein in brain is the defining feature several neurodegenerative diseases called tauopathies, including Alzheimer’s disease (AD). In AD, this pathological change reflected by highly specific cerebrospinal fluid (CSF) biomarkers, both phosphorylated non-phosphorylated variants. Interestingly, despite pathology being at core all CSF biomarkers remain unchanged certain e.g., progressive supranuclear palsy (PSP), Pick’s...
Abstract Alzheimer’s disease (AD) and other tauopathies are characterized by the aggregation of tau into soluble insoluble forms (including tangles neuropil threads). In humans, a fraction both phosphorylated non-phosphorylated N-terminal to mid-domain species, secreted cerebrospinal fluid (CSF). Some these CSF species can be measured as diagnostic prognostic biomarkers, starting from early stages disease. While in animal models AD pathology, aggregates have been shown disrupt neuronal...
Abstract Synaptic pathology is a central event in Alzheimer’s disease (AD) and other neurodegenerative conditions, investigation of synaptic proteins can provide valuable tools to follow dysfunction loss these diseases. Neuroligin-1 (Nlgn1) postsynaptic cell adhesion protein, important for synapse stabilization formation. Nlgn1 has been connected cognitive disorders, specifically AD, as target the synaptotoxic effect amyloid-β (Aβ) oligomers Aβ fibrils. To address changes expression human...
Neurogranin (Ng) is a small 7.6 kDa postsynaptic protein that has been detected at elevated concentrations in cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD), both as full-length molecule and fragments from its C-terminal half. Ng involved calcium (Ca) signal transduction memory formation via binding to calmodulin Ca-dependent manner. The mechanism secretion neurons CSF currently unknown, but enzymatic cleavage may be relevance. Therefore, the aim study was identify...
Abstract Objective The purpose of this study was to examine the levels cerebrospinal fluid (CSF) apolipoprotein E (apoE) species in Alzheimer’s disease (AD) patients. Methods We analyzed two CSF cohorts AD and control individuals expressing different APOE genotypes. Moreover, samples from TgF344-AD rat model were included. Samples run native- SDS-PAGE under reducing or non-reducing conditions (with without β-mercaptoethanol). Immunoprecipitation combined with mass spectrometry western...
Abstract Alzheimer’s disease (AD) is characterized by extracellular amyloid plaques containing amyloid-β (Aβ) peptides, intraneuronal neurofibrillary tangles, neuropil threads, and dystrophic neurites surrounding composed of hyperphosphorylated tau protein (pTau). Aβ can also deposit in blood vessel walls leading to cerebral angiopathy (CAA). While AD brains are constant, CAA varies among cases. The study focuses on differences observed between rare poorly studied patient groups with APP...
Abstract Tau pathology is a hallmark of several neurodegenerative diseases, including frontotemporal dementia and Alzheimer’s disease. However, the sequence events form tau that confers toxicity are still unclear, due in large part to lack physiological models tauopathy initiation progression which test hypotheses. We have developed series targeted mice expressing frontotemporal-dementia-causing mutations humanized MAPT gene investigate earliest stages tauopathy. Int10+3G>A...
Blood phosphorylated tau (p-tau) biomarkers, including p-tau217, show high associations with Alzheimer's disease (AD) neuropathologic change and clinical stage. Certain plasma p-tau217 assays recognize forms additionally at threonine-212, but the contribution of p-tau212 alone to AD is unknown. We developed a blood-based immunoassay that specific without cross-reactivity p-tau217. Thereafter, we examined diagnostic utility p-tau212. In five cohorts (n=388 participants), showed performances...
BackgroundSynaptic proteins are increasingly studied as biomarkers for synaptic dysfunction and loss, which early central events in Alzheimer's disease (AD) strongly correlate with the degree of cognitive decline. In this study, we specifically investigated binding partners neurexin (NRXN) neuroligin (Nlgn) proteins, to assess their biomarker's potential.Methodswe developed a parallel reaction monitoring mass spectrometric method simultaneous quantification NRXNs Nlgns cerebrospinal fluid...
Abstract Excess brain cholesterol is strongly implicated in the pathogenesis of Alzheimer’s disease (AD). Here we evaluated how presence a cholesterol-binding site (CBS) transmembrane and juxtamembrane regions amyloid precursor protein (APP) regulates its processing. We generated nine point mutations APP gene, changing charge and/or hydrophobicity amino-acids which were previously shown as part CBS. Most triggered reduction amyloid-β peptides Aβ40 Aβ42 secretion from transiently transfected...
Neurogranin (Ng) is a 78 amino acid neuronal protein and biomarker candidate for Alzheimer's disease (AD). Ng has been suggested to bind calmodulin phosphatidic via its centrally located IQ domain. cleaved within this functionally important domain, yielding the majority of fragments identified in cerebrospinal fluid (CSF), suggesting that cleavage may be mechanism regulate function. Up now, shown present CSF as both C-terminal well full-length protein. To obtain an overview different...
Abstract Tau pathology is a hallmark feature of several neurodegenerative diseases including frontotemporal dementia (FTD) spectrum and Alzheimer’s disease. The accumulation pathological tau linked to cognitive impairment. However, the sequence events form that confers toxicity are still unclear, due lack physiological models tauopathy initiation progression in which test hypotheses. We have developed series novel, targeted mice expressing FTD-causing mutations humanized MAPT gene...
Introducing heterozygous humanized tau to App
Abstract Background Knowledge of the chemical composition amyloid plaques and tau tangles at earlier stages Alzheimer’s disease (AD) pathology is sparse. This due to limited access human brain during life AD pathophysiology technical limitations in quantifying species a subcellular level. Understanding tangles, how rapidly they grow what factors drive growth important for developing refining therapeutics. We vivo cortical biopsy samples from individuals undergoing surgery, aiming provide...
Abstract Alzheimer’s disease (AD) and other tauopathies are characterized by the aggregation of tau into soluble insoluble forms (including tangles neuropil threads). In humans, a fraction both phosphorylated non-phosphorylated N-terminal to mid-domain species, including aggregated forms, secreted cerebrospinal fluid (CSF). Some these CSF species can be measured as diagnostic prognostic biomarkers, starting from early stages disease. While in animal models AD pathology, aggregates have been...
Abstract Background In the Insight 46 sub‐study of 1946 British birth cohort we investigated concordance baseline plasma biomarkers (age 71) with cerebral amyloid PET status at two time‐points (ages 71 and 73). Method Baseline samples were tested using Simoa (Quanterix) commercial (NfL, GFAP, Aβ42, Aβ40, p‐tau181V2) homebrew digital immunoassays (p‐tau181, p‐tau231: University Gothenburg; NT1 tau: Harvard University). Logistic regression ROC analysis used to assess single each timepoint,...
Neurogranin (Ng) is a small 7.5 kD postsynaptic protein that has been detected at elevated concentrations in cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD), both as full length molecule well fragments representing its C-terminal half. The Ng-peptide pattern CSF suggests two main cleavage regions on the Ng molecule, namely one central and near end Ng. present work was aimed identifying enzymes generating this pattern. Two quenched fluorogenic peptides based sequences were...
Neuroligin 1 (NLGN-1) is a post-synaptic cell adhesion protein specifically expressed at glutamatergic synapses [1]. It interacts with the pre-synaptic molecule neurexin-1β to promote across synaptic cleft, beyond promoting clustering of receptors and channels, important for plasticity [2]. NLGN-1 has been connected Alzheimer's disease (AD), as its extracellular part seems interact A3β oligomers (Aβo), targeting this synaptotoxic form Aβ [3, 4]. Here we examine first time potential biomarker...