A5080487735- Alzheimer's disease research and treatments
- Amyotrophic Lateral Sclerosis Research
- Dementia and Cognitive Impairment Research
- Parkinson's Disease Mechanisms and Treatments
- Neurological diseases and metabolism
- Neurobiology of Language and Bilingualism
- EEG and Brain-Computer Interfaces
- Prion Diseases and Protein Misfolding
- Genetics and Neurodevelopmental Disorders
- Functional Brain Connectivity Studies
- Genomics and Rare Diseases
- Genetic Neurodegenerative Diseases
- Neurogenetic and Muscular Disorders Research
- Neurological disorders and treatments
- Lysosomal Storage Disorders Research
- Neurological Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Cerebrovascular and genetic disorders
- Epigenetics and DNA Methylation
- Advanced Neuroimaging Techniques and Applications
- Glycogen Storage Diseases and Myoclonus
- Cholinesterase and Neurodegenerative Diseases
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Cholesterol and Lipid Metabolism
- Reading and Literacy Development
University of Antwerp
2016-2025
Antwerp University Hospital
2014-2025
VIB-UAntwerp Center for Molecular Neurology
2012-2024
University of Alberta
2024
Pasqual Maragall Foundation
2024
Ghent University Hospital
2012-2022
AZ Sint-Jan
2017-2021
Bunge & Born Foundation
2021
Ghent University
2020
Austin Health
2018
Abstract Hexanucleotide repeat expansions in C9orf72 are the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) (c9ALS/FTD). Unconventional translation these repeats produces dipeptide proteins (DPRs) that may neurodegeneration. We performed a modifier screen Drosophila discovered critical role for importins exportins, Ran-GTP cycle regulators, nuclear pore components arginine methylases mediating DPR toxicity. These findings provide evidence an...
Pathological expansion of a G4C2 repeat, located in the 5' regulatory region C9orf72, is most common genetic cause frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). C9orf72 patients have highly variable onset ages suggesting presence modifying factors and/or anticipation. We studied 72 Belgian index with FTLD, FTLD–ALS or ALS 61 relatives repeat expansion. assessed effect size on age, role anticipation methylation promoter activity. sizes varied blood between...
The current study investigated the effects of bilingualism on clinical manifestation Alzheimer's disease (AD) in a European sample patients. We assessed all incoming AD patients two university hospitals within specified timeframe. Sixty-nine monolinguals and 65 bilinguals diagnosed with probable were compared for time diagnosis. influence other potentially interacting variables was also examined. Results indicated significant delay 4.6 years 4.8 Our therefore strengthens claim that...
<h3>Objective:</h3> To assess the genetic contribution of <i>TBK1</i>, a gene implicated in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and FTD-ALS, Belgian FTD ALS patient cohorts containing significant part genetically unresolved patients. <h3>Methods:</h3> We sequenced <i>TBK1</i> hospital-based cohort 482 unrelated patients with FTD-ALS 147 an extended family DR158. followed up mutation carriers by segregation studies, transcript protein expression analysis,...
Mutations in the gene coding for Sequestosome 1 (SQSTM1) have been genetically associated with amyotrophic lateral sclerosis (ALS) and Paget disease of bone. In present study, we analyzed SQSTM1 sequence mutations an extended cohort 1,808 patients frontotemporal lobar degeneration (FTLD), ascertained within European Early-Onset Dementia consortium. As control dataset, sequenced 1,625 individuals whole-exome data 2,274 German (total n = 3,899). Association rare was calculated a meta-analysis...
We identified in a cohort of patients with frontotemporal dementia (n = 481) or amyotrophic lateral sclerosis 147), 10 index carrying TBK1 loss function mutation reducing expression by 50%. Here, we describe the clinical and pathological characteristics six their affected relatives mutation. Six carriers were diagnosed dementia, seven sclerosis, one both phenotypes two unspecified. The mean age at onset all 16 was 62.1 ± 8.9 years (range 41–73) disease duration 4.7 4.5 1–13). had shorter...
Diagnosis of dementia with Lewy bodies (DLB) is challenging and specific biofluid biomarkers are highly needed. We employed proximity extension-based assays to measure 665 proteins in the cerebrospinal fluid (CSF) from patients DLB (n = 109), Alzheimer´s disease (AD, n 235) cognitively unimpaired controls 190). identified over 50 CSF dysregulated DLB, enriched myelination processes among others. The dopamine biosynthesis enzyme DDC was strongest protein, could efficiently discriminate AD...
To characterize patients with frontotemporal lobar degeneration (FTLD) a repeat expansion mutation in the gene C9orf72, and to determine whether there are differences clinical presentation compared FTLD carriers of GRN or MAPT without mutation.Patient series.Dementia clinics Flanders, Belgium.Two hundred seventy-five genetically phenotypically thoroughly characterized FTLD.Clinical demographic characteristics 26 C9orf72 mutation, as well familial sporadic mutation.C9orf72 developed at an...
Mutation screening and phenotypic profiling of 2 amyotrophic lateral sclerosis–(ALS) frontotemporal dementia–(FTD) associated genes, CHCHD10 TUBA4A, were performed in a Belgian cohort 459 FTD, 28 FTD-ALS, 429 ALS patients. In CHCHD10, we identified novel nonsense mutation (p.Gln108*) patient with atypical clinical FTD pathology-confirmed Parkinson's disease (1/459, 0.22%) leading to loss transcript. We further observed 3 previously described missense variants (p.Pro34Ser, p.Pro80Leu,...
The most common form of autosomal recessive hereditary spastic paraplegia is caused by mutations in the SPG11/KIAA1840 gene on chromosome 15q. nature vast majority SPG11 found to date suggests a loss-of-function mechanism encoded protein, spatacsin. phenotype is, cases, characterized progressive spasticity with neuropathy, cognitive impairment and thin corpus callosum brain MRI. Full neuropathological characterization has not been reported despite description >100 mutations. We describe here...
<h3>Importance</h3> Patients carrying a<i>C9orf72</i>repeat expansion leading to frontotemporal dementia and/or amyotrophic lateral sclerosis have highly variable ages at onset of disease, suggesting the presence modifying factors. <h3>Objective</h3> To provide clinical-based evidence for disease anticipation in families by analyzing age onset, duration, and death successive generations. <h3>Design, Setting, Participants</h3> This cohort study was performed from June 16, 2000, 1, 2016, 36...
We explored the diagnostic performance of cerebrospinal fluid (CSF) biomarkers in allowing differentiation between frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD), as well FTLD pathological subtypes.CSF levels routine AD (phosphorylated tau (p-tau181), total (t-tau), amyloid-beta (Aβ)1-42) neurofilament proteins, progranulin both CSF serum were quantified definite (n = 46), clinical 45), cognitively healthy controls 20). subgroups defined by genetic carrier status...
Emerging evidence suggested a converging mechanism in neurodegenerative brain diseases (NBD) involving early neuronal network dysfunctions and alterations the homeostasis of firing as culprits neurodegeneration. In this study, we used paired-end short-read direct long-read whole genome sequencing to investigate an unresolved autosomal dominant dementia family significantly linked 7q36. We identified validated chromosomal inversion ca. 4 Mb, segregating on disease haplotype disrupting coding...
Abstract Alzheimer’s disease CSF biomarkers 42 amino acid long amyloid-β peptide (Aβ1–42), total tau protein (T-tau), and phosphorylated at threonine 181 (P-tau181) are considered surrogate of pathology, significantly improve diagnostic accuracy. Their ability to reflect neuropathological changes later in the course is not well characterized. This study aimed assess potential measured mid late stage post-mortem changes. Individuals were selected from two autopsy cohorts patients Antwerp...
Abstract The biological definition of Alzheimer’s disease using CSF biomarkers requires abnormal levels both amyloid (A) and tau (T). However, corresponding cutoffs may not always reflect the presence or absence pathology. Previous studies suggest that up to 32% individuals with autopsy-confirmed show normal p-tau in vivo, but these are sparse had small sample sizes. Therefore, three independent autopsy cohorts, we studied whether A+T− excluded based on autopsy. We included 215 individuals,...
Routinely prescribed psychoactive drugs in behavioral variant frontotemporal dementia (FTD) for improvement of (non)cognitive symptoms are primarily based on monoamine replacement or augmentation strategies. These were, however, initially intended to symptomatically treat other degenerative, behavi oral, personality disorders, and thus lack disease specificity. Moreover, current knowledge brain monoaminergic neurotransmitter deficiencies this presenile disorder is scarce, particularly with...
Dementia with Lewy bodies (DLB) and Parkinson's disease (PD) are clinically, pathologically etiologically disorders embedded in the body (LBD) continuum, characterized by neuronal α-synuclein pathology. Rare homozygous compound heterozygous premature termination codon (PTC) mutations Vacuolar Protein Sorting 13 homolog C gene (VPS13C) associated early-onset recessive PD. We observed two siblings age (< 45) autopsy confirmed DLB, missense VPS13C, p.Trp395Cys p.Ala444Pro, inherited from their...
Abstract Partial phenotypic overlap has been suggested between multiple system atrophy (MSA) and spinocerebellar ataxia 27B, the autosomal dominant caused by an intronic GAA•TTC repeat expansion in FGF14. This study investigated frequency of FGF14 clinically diagnosed pathologically confirmed cases. We screened 657 cases (193 464 confirmed) 1,003 controls. The locus was genotyped using long-range PCR bidirectional repeat-primed PCRs, expansions were with targeted long-read Oxford Nanopore...
We evaluated the genetic impact of amyotrophic lateral sclerosis (ALS) risk gene never in mitosis a–related kinase 1 (NEK1) a Belgian cohort 278 patients with ALS (n = 245) or frontotemporal dementia (ALS-FTD, n 33) and 609 control individuals. identified 2 carrying loss-of-function (LOF) mutation, p.Leu854Tyrfs*2 p.Tyr871Valfs*17, that was absent group. A third LOF variant p.Ser1036* present sibs familial but also an unrelated person. Missense variants were common both (3.6%) controls...
<h3>Objective:</h3> To generate a clinical and pathologic phenotype of patients carrying rare loss-of-function mutations in <i>ABCA7</i>, identified Belgian Alzheimer patient cohort an autosomal dominant family. <h3>Methods:</h3> We performed retrospective review available data records, medical results CSF analyses neuroimaging studies, neuropathology data. <h3>Results:</h3> The mean onset age the mutation carriers (n = 22) was 73.4 ± 8.4 years with wide range 36 (54–90) years, which...