A5031573702- Alzheimer's disease research and treatments
- Mitochondrial Function and Pathology
- Cell death mechanisms and regulation
- Trace Elements in Health
- Cholinesterase and Neurodegenerative Diseases
- Dementia and Cognitive Impairment Research
- Inflammasome and immune disorders
- Advanced Proteomics Techniques and Applications
- Neurological diseases and metabolism
- Phytoestrogen effects and research
- Neurological Disease Mechanisms and Treatments
- Cellular transport and secretion
- Genetic Associations and Epidemiology
- Neuroinflammation and Neurodegeneration Mechanisms
- Machine Learning in Bioinformatics
- Prion Diseases and Protein Misfolding
- Telomeres, Telomerase, and Senescence
- Tryptophan and brain disorders
- Amyotrophic Lateral Sclerosis Research
- Calcium signaling and nucleotide metabolism
- Amino Acid Enzymes and Metabolism
- Bioinformatics and Genomic Networks
KU Leuven
2019-2024
VIB-KU Leuven Center for Brain & Disease Research
2019-2024
Vlaams Instituut voor Biotechnologie
2022-2024
Abstract Aging is the main risk factor for Alzheimer’s disease (AD) and other neurodegenerative pathologies, but molecular cellular changes underlying pathological aging of nervous system are poorly understood. AD pathology seems to correlate with appearance cells that become senescent due progressive accumulation insults causing DNA damage. Senescence has also been shown reduce autophagic flux, a mechanism involved in clearing damaged proteins from cell, such impairment linked pathogenesis....
Necroptosis is a regulated form of cell death that has been observed in Alzheimer’s disease (AD) along with the classical pathological hallmark lesions amyloid plaques and Tau neurofibrillary tangles. To understand neurodegenerative process AD, we studied role necroptosis mouse models primary neurons. Using immunohistochemistry, demonstrated activated necroptosis-related proteins transgenic mice developing pathology neurons from precursor protein (APP)–Tau double treated phosphorylated seeds...
It has become evident that Alzheimer's Disease (AD) is not only linked to its hallmark lesions-amyloid plaques and neurofibrillary tangles (NFTs)-but also other co-occurring pathologies. This may lead synergistic effects of the respective cellular molecular players, resulting in neuronal death. One these co-pathologies accumulation phosphorylated transactive-response DNA binding protein 43 (pTDP-43) as cytoplasmic inclusions, currently considered represent limbic-predominant age-related...
Granulovacuolar degeneration (GVD) in Alzheimer's disease (AD) involves the necrosome, which is a protein complex consisting of phosphorylated receptor-interacting kinase 1 (pRIPK1), pRIPK3 and mixed lineage domain-like (pMLKL). Necrosome-positive GVD was associated with neuron loss AD. recently linked to C9ORF72 mutation amyotrophic lateral sclerosis (ALS) frontotemporal lobar transactive response DNA-binding (TDP-43) pathology (FTLD-TDP). Therefore, we investigated whether cases...
Abstract Proteome profile changes in Alzheimer's disease (AD) brains have been reported. However, it is unclear whether they represent a continuous process, or there sequential involvement of distinct proteins. To address this question, we used mass spectrometry. We analyzed soluble, dispersible, sodium dodecyl sulfate, and formic acid fractions neocortex homogenates (mainly Brodmann area 17‐19) from 18 pathologically diagnosed preclinical AD, 17 symptomatic cases without signs...
Abstract Alzheimer’s disease is neuropathologically characterized by the deposition of amyloid β-peptide (Aβ) as plaques. Aβ plaque pathology starts in neocortex before it propagates into further brain regions. Moreover, aggregates undergo maturation indicated occurrence post-translational modifications. Here, we show that propagation plaques led presumably non-modified followed aggregate maturation. This sequence was seen human brains and precursor protein transgenic mice receiving...
Abstract Background As neurodegenerative diseases advance, postmitotic neurons are affected by disturbed proteostasis and the accumulation of misfolded proteins. This renders sensitive to cell death, ultimately leading progressive neuron loss. Multiple studies show involvement distinct pathways regulated death (RCD) in diseases, such as necroptosis. In human AD, activation necroptosis has been shown contribute process. However, despite considerable research efforts, it is still not clear...
Abstract Background Alzheimer’s disease (AD) is a heterogenous with strong heritability. Genetic studies are of irreplaceable value in elucidating the mechanisms that underly this disease. The classical genome‐wide association (GWAS) rely on ever‐increasing sample sizes and utilize clinical AD diagnosis to investigate genetic risk. Here, we aim eliminate phenotypic heterogeneity by performing GWAS deeply phenotyped neuropathological cohort. Method Phenotypic data regarding hallmark co‐morbid...
Abstract Background Alzheimer’s disease (AD) is characterized by pathological processes such as β‐amyloid (Aβ) plaques, neurofibrillary tangles (NFT), cytoplasmic granulovacuolar degeneration (GVD) lesions and neuronal loss that underpin cognitiveand behavioral alterations. Necroptosis, a programmed form of cell death defined the assembly necrosome complex composed phosphorylated proteins (pRIPK1, pRIPK3 pMLKL), has recently been shown to be involved in AD. Method To determine...
Abstract Background Neurodegenerative brain diseases (NBDs) ultimately result in neuronal loss and subsequent cognitive decline. In Alzheimer’s disease, tau neurofibrillary tangles (NFT) amyloid plaques are considered as the hallmark lesions, but there a number of other distinct features that not exclusive to AD do occur certain extent NBDs. Method We extracted DNA from cohort 382 post‐mortem brains NBD patients controls with detailed neuropathological characterization. Genotyping 85 genetic...
Abstract Background Neuronal death is the result of neurodegenerative process in Alzheimer’s disease (AD). Both histopathological hallmark lesions AD, i.e., amyloid plaques and neurofibrillary tangles, are associated with reduced numbers neurons brain. To model AD‐like neuronal death, mouse models transgenic overexpression precursor protein (APP) tau can be used. Recently, necroptotic cell pathway was found to activated AD In this context, necrosome granulovacuolar degeneration (GVD)...
Abstract Background Proteomic profile changes have been reported in the brains from individuals having Alzheimer’s disease. However, it is not yet clear whether they represent a continuous process mild to severe changes, or proteins become involved step‐by‐step hierarchal manner. Additionally, previous studies, cases with initial Aβ plaque and NFT pathology were considered as controls, brain homogenates separated into distinct fractions. Therefore, there gap of knowledge regarding steps AD...
Abstract Background Amyloid β‐plaques are a hallmark lesion of Alzheimer’s disease (AD) and consist aggregates the amyloid β‐peptide (Aβ). Aβ peptides can undergo posttranslational modifications, including N‐terminal truncation with subsequent pyroglutamate formation at glutamate 3, phosphorylation serine 8, leading to N3pE pSer8 , respectively. These posttranslationally modified forms present in brain addition non‐modified Aβ. During development composition changes from without detectable...