ArticleNeurology2015
Loss of TBK1 is a frequent cause of frontotemporal dementia in a Belgian cohort.
Open access · bronzeAbstract read
In one paragraph
Article in Neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed, 1 pooled it
13.3field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 173 citations in OpenAlex.
- Pooled it
- A new era of genome-wide association studies in the field of Alzheimer's disease and overlapping co-pathologies: lessons learned from a neuropathology-centered approach.Acta neuropathologica · 2026Review
- Clinical and immunological characterization of a child with a homozygous TBK1 kinase-domain truncation.Immunologic research · 2026Article
- Review
- Minding the gates: dual cell-autonomous and non-cell-autonomous mechanisms of TBK1 in ALS/FTD.Frontiers in neuroscience · 2026Review
- Phospho-proteome profiling in human neurons reveals targets of TBK1 in ALS/FTD-associated autophagy networks.Cell reports · 2025Article
- Exploring TANK-Binding Kinase 1 in Amyotrophic Lateral Sclerosis: From Structural Mechanisms to Machine Learning-Guided Therapeutics.Life (Basel, Switzerland) · 2025Review
- TFEB overexpression alleviates autophagy-lysosomal deficits caused by progranulin insufficiency.Scientific reports · 2025Article
- TBK1 and IKKε prevent premature cell death by limiting the activity of both RIPK1 and NLRP3 death pathways.Science advances · 2025Article
- TBK1 mutation and its role in frontotemporal dementia and amyotrophic lateral sclerosis in Brazilian families.Dementia & neuropsychologia · 2025Review
- The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).Autophagy reports · 2025Review
- Early disruption of the CREB pathway drives dendritic morphological alterations in FTD/ALS cortical neurons.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Lysosome quality control in health and neurodegenerative diseases.Cellular & molecular biology letters · 2024Review
- Lysosomal TBK1 responds to amino acid availability to relieve Rab7-dependent mTORC1 inhibition.The EMBO journal · 2024Article
- Clinicopathologic Characterization of 2 Individuals WithNeurology. Genetics · 2024Article
- Genetic and clinical landscape of Chinese frontotemporal dementia: dominance of TBK1 and OPTN mutations.Alzheimer's research & therapy · 2024Article
- Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS.Nature medicine · 2024Article
- Endo-lysosomal dysfunction in neurodegenerative diseases: opinion on current progress and future direction in the use of exosomes as biomarkers.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Lysosomal TBK1 Responds to Amino Acid Availability to Relieve Rab7-Dependent mTORC1 Inhibition.bioRxiv : the preprint server for biology · 2023Article
- Pharmacogenomics of Dementia: Personalizing the Treatment of Cognitive and Neuropsychiatric Symptoms.Genes · 2023Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 6 institutions in 1 country.
Ilse GijselinckFrom the Department of Molecular Genetics (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., M.C., C.V.B.), VIB, Antwerp; Institute Born-Bunge (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., S.E., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., P.C., P.P.D.D., J.-J.M., M.C., C.V.B.), University of Antwerp; the Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; the Department of Neurology and Memory Clinic (S.E., P.P.D.D.), Hospital Network Antwerp Middelheim and Hoge Beuken; the Brain and Emotion Laboratory, Department of Psychiatry (M.V.), SWITCH Laboratory, VIB (G.D.B., F.R.), and Laboratory for Cognitive Neurology, Department of Neurology (R.V.), University of Leuven; the Department of Neurology (M.V., R.V.), University Hospitals Leuven, Gasthuisberg; and the Department of Neurology (P.D.J., P.C.), Antwerp University Hospital, Edegem, Belgium. P.P.D.D. is also affiliated with the Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, the Netherlands.
Sara Van MosseveldeFrom the Department of Molecular Genetics (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., M.C., C.V.B.), VIB, Antwerp; Institute Born-Bunge (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., S.E., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., P.C., P.P.D.D., J.-J.M., M.C., C.V.B.), University of Antwerp; the Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; the Department of Neurology and Memory Clinic (S.E., P.P.D.D.), Hospital Network Antwerp Middelheim and Hoge Beuken; the Brain and Emotion Laboratory, Department of Psychiatry (M.V.), SWITCH Laboratory, VIB (G.D.B., F.R.), and Laboratory for Cognitive Neurology, Department of Neurology (R.V.), University of Leuven; the Department of Neurology (M.V., R.V.), University Hospitals Leuven, Gasthuisberg; and the Department of Neurology (P.D.J., P.C.), Antwerp University Hospital, Edegem, Belgium. P.P.D.D. is also affiliated with the Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, the Netherlands.
Julie van der ZeeFrom the Department of Molecular Genetics (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., M.C., C.V.B.), VIB, Antwerp; Institute Born-Bunge (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., S.E., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., P.C., P.P.D.D., J.-J.M., M.C., C.V.B.), University of Antwerp; the Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; the Department of Neurology and Memory Clinic (S.E., P.P.D.D.), Hospital Network Antwerp Middelheim and Hoge Beuken; the Brain and Emotion Laboratory, Department of Psychiatry (M.V.), SWITCH Laboratory, VIB (G.D.B., F.R.), and Laboratory for Cognitive Neurology, Department of Neurology (R.V.), University of Leuven; the Department of Neurology (M.V., R.V.), University Hospitals Leuven, Gasthuisberg; and the Department of Neurology (P.D.J., P.C.), Antwerp University Hospital, Edegem, Belgium. P.P.D.D. is also affiliated with the Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, the Netherlands.
Anne SiebenFrom the Department of Molecular Genetics (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., M.C., C.V.B.), VIB, Antwerp; Institute Born-Bunge (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., S.E., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., P.C., P.P.D.D., J.-J.M., M.C., C.V.B.), University of Antwerp; the Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; the Department of Neurology and Memory Clinic (S.E., P.P.D.D.), Hospital Network Antwerp Middelheim and Hoge Beuken; the Brain and Emotion Laboratory, Department of Psychiatry (M.V.), SWITCH Laboratory, VIB (G.D.B., F.R.), and Laboratory for Cognitive Neurology, Department of Neurology (R.V.), University of Leuven; the Department of Neurology (M.V., R.V.), University Hospitals Leuven, Gasthuisberg; and the Department of Neurology (P.D.J., P.C.), Antwerp University Hospital, Edegem, Belgium. P.P.D.D. is also affiliated with the Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, the Netherlands.
Stéphanie PhiltjensFrom the Department of Molecular Genetics (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., M.C., C.V.B.), VIB, Antwerp; Institute Born-Bunge (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., S.E., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., P.C., P.P.D.D., J.-J.M., M.C., C.V.B.), University of Antwerp; the Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; the Department of Neurology and Memory Clinic (S.E., P.P.D.D.), Hospital Network Antwerp Middelheim and Hoge Beuken; the Brain and Emotion Laboratory, Department of Psychiatry (M.V.), SWITCH Laboratory, VIB (G.D.B., F.R.), and Laboratory for Cognitive Neurology, Department of Neurology (R.V.), University of Leuven; the Department of Neurology (M.V., R.V.), University Hospitals Leuven, Gasthuisberg; and the Department of Neurology (P.D.J., P.C.), Antwerp University Hospital, Edegem, Belgium. P.P.D.D. is also affiliated with the Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, the Netherlands.
Bavo HeemanFrom the Department of Molecular Genetics (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., M.C., C.V.B.), VIB, Antwerp; Institute Born-Bunge (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., S.E., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., P.C., P.P.D.D., J.-J.M., M.C., C.V.B.), University of Antwerp; the Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; the Department of Neurology and Memory Clinic (S.E., P.P.D.D.), Hospital Network Antwerp Middelheim and Hoge Beuken; the Brain and Emotion Laboratory, Department of Psychiatry (M.V.), SWITCH Laboratory, VIB (G.D.B., F.R.), and Laboratory for Cognitive Neurology, Department of Neurology (R.V.), University of Leuven; the Department of Neurology (M.V., R.V.), University Hospitals Leuven, Gasthuisberg; and the Department of Neurology (P.D.J., P.C.), Antwerp University Hospital, Edegem, Belgium. P.P.D.D. is also affiliated with the Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, the Netherlands.
Sebastiaan EngelborghsFrom the Department of Molecular Genetics (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., M.C., C.V.B.), VIB, Antwerp; Institute Born-Bunge (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., S.E., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., P.C., P.P.D.D., J.-J.M., M.C., C.V.B.), University of Antwerp; the Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; the Department of Neurology and Memory Clinic (S.E., P.P.D.D.), Hospital Network Antwerp Middelheim and Hoge Beuken; the Brain and Emotion Laboratory, Department of Psychiatry (M.V.), SWITCH Laboratory, VIB (G.D.B., F.R.), and Laboratory for Cognitive Neurology, Department of Neurology (R.V.), University of Leuven; the Department of Neurology (M.V., R.V.), University Hospitals Leuven, Gasthuisberg; and the Department of Neurology (P.D.J., P.C.), Antwerp University Hospital, Edegem, Belgium. P.P.D.D. is also affiliated with the Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, the Netherlands.
Mathieu VandenbulckeFrom the Department of Molecular Genetics (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., M.C., C.V.B.), VIB, Antwerp; Institute Born-Bunge (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., S.E., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., P.C., P.P.D.D., J.-J.M., M.C., C.V.B.), University of Antwerp; the Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; the Department of Neurology and Memory Clinic (S.E., P.P.D.D.), Hospital Network Antwerp Middelheim and Hoge Beuken; the Brain and Emotion Laboratory, Department of Psychiatry (M.V.), SWITCH Laboratory, VIB (G.D.B., F.R.), and Laboratory for Cognitive Neurology, Department of Neurology (R.V.), University of Leuven; the Department of Neurology (M.V., R.V.), University Hospitals Leuven, Gasthuisberg; and the Department of Neurology (P.D.J., P.C.), Antwerp University Hospital, Edegem, Belgium. P.P.D.D. is also affiliated with the Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, the Netherlands.
Greet De BaetsFrom the Department of Molecular Genetics (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., M.C., C.V.B.), VIB, Antwerp; Institute Born-Bunge (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., S.E., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., P.C., P.P.D.D., J.-J.M., M.C., C.V.B.), University of Antwerp; the Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; the Department of Neurology and Memory Clinic (S.E., P.P.D.D.), Hospital Network Antwerp Middelheim and Hoge Beuken; the Brain and Emotion Laboratory, Department of Psychiatry (M.V.), SWITCH Laboratory, VIB (G.D.B., F.R.), and Laboratory for Cognitive Neurology, Department of Neurology (R.V.), University of Leuven; the Department of Neurology (M.V., R.V.), University Hospitals Leuven, Gasthuisberg; and the Department of Neurology (P.D.J., P.C.), Antwerp University Hospital, Edegem, Belgium. P.P.D.D. is also affiliated with the Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, the Netherlands.
Veerle BäumerFrom the Department of Molecular Genetics (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., M.C., C.V.B.), VIB, Antwerp; Institute Born-Bunge (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., S.E., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., P.C., P.P.D.D., J.-J.M., M.C., C.V.B.), University of Antwerp; the Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; the Department of Neurology and Memory Clinic (S.E., P.P.D.D.), Hospital Network Antwerp Middelheim and Hoge Beuken; the Brain and Emotion Laboratory, Department of Psychiatry (M.V.), SWITCH Laboratory, VIB (G.D.B., F.R.), and Laboratory for Cognitive Neurology, Department of Neurology (R.V.), University of Leuven; the Department of Neurology (M.V., R.V.), University Hospitals Leuven, Gasthuisberg; and the Department of Neurology (P.D.J., P.C.), Antwerp University Hospital, Edegem, Belgium. P.P.D.D. is also affiliated with the Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, the Netherlands.
Ivy CuijtFrom the Department of Molecular Genetics (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., M.C., C.V.B.), VIB, Antwerp; Institute Born-Bunge (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., S.E., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., P.C., P.P.D.D., J.-J.M., M.C., C.V.B.), University of Antwerp; the Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; the Department of Neurology and Memory Clinic (S.E., P.P.D.D.), Hospital Network Antwerp Middelheim and Hoge Beuken; the Brain and Emotion Laboratory, Department of Psychiatry (M.V.), SWITCH Laboratory, VIB (G.D.B., F.R.), and Laboratory for Cognitive Neurology, Department of Neurology (R.V.), University of Leuven; the Department of Neurology (M.V., R.V.), University Hospitals Leuven, Gasthuisberg; and the Department of Neurology (P.D.J., P.C.), Antwerp University Hospital, Edegem, Belgium. P.P.D.D. is also affiliated with the Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, the Netherlands.
Marleen Van den BroeckFrom the Department of Molecular Genetics (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., M.C., C.V.B.), VIB, Antwerp; Institute Born-Bunge (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., S.E., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., P.C., P.P.D.D., J.-J.M., M.C., C.V.B.), University of Antwerp; the Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; the Department of Neurology and Memory Clinic (S.E., P.P.D.D.), Hospital Network Antwerp Middelheim and Hoge Beuken; the Brain and Emotion Laboratory, Department of Psychiatry (M.V.), SWITCH Laboratory, VIB (G.D.B., F.R.), and Laboratory for Cognitive Neurology, Department of Neurology (R.V.), University of Leuven; the Department of Neurology (M.V., R.V.), University Hospitals Leuven, Gasthuisberg; and the Department of Neurology (P.D.J., P.C.), Antwerp University Hospital, Edegem, Belgium. P.P.D.D. is also affiliated with the Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, the Netherlands.
Karin PeetersFrom the Department of Molecular Genetics (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., M.C., C.V.B.), VIB, Antwerp; Institute Born-Bunge (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., S.E., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., P.C., P.P.D.D., J.-J.M., M.C., C.V.B.), University of Antwerp; the Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; the Department of Neurology and Memory Clinic (S.E., P.P.D.D.), Hospital Network Antwerp Middelheim and Hoge Beuken; the Brain and Emotion Laboratory, Department of Psychiatry (M.V.), SWITCH Laboratory, VIB (G.D.B., F.R.), and Laboratory for Cognitive Neurology, Department of Neurology (R.V.), University of Leuven; the Department of Neurology (M.V., R.V.), University Hospitals Leuven, Gasthuisberg; and the Department of Neurology (P.D.J., P.C.), Antwerp University Hospital, Edegem, Belgium. P.P.D.D. is also affiliated with the Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, the Netherlands.
Maria MattheijssensFrom the Department of Molecular Genetics (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., M.C., C.V.B.), VIB, Antwerp; Institute Born-Bunge (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., S.E., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., P.C., P.P.D.D., J.-J.M., M.C., C.V.B.), University of Antwerp; the Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; the Department of Neurology and Memory Clinic (S.E., P.P.D.D.), Hospital Network Antwerp Middelheim and Hoge Beuken; the Brain and Emotion Laboratory, Department of Psychiatry (M.V.), SWITCH Laboratory, VIB (G.D.B., F.R.), and Laboratory for Cognitive Neurology, Department of Neurology (R.V.), University of Leuven; the Department of Neurology (M.V., R.V.), University Hospitals Leuven, Gasthuisberg; and the Department of Neurology (P.D.J., P.C.), Antwerp University Hospital, Edegem, Belgium. P.P.D.D. is also affiliated with the Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, the Netherlands.
Frederic RousseauFrom the Department of Molecular Genetics (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., M.C., C.V.B.), VIB, Antwerp; Institute Born-Bunge (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., S.E., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., P.C., P.P.D.D., J.-J.M., M.C., C.V.B.), University of Antwerp; the Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; the Department of Neurology and Memory Clinic (S.E., P.P.D.D.), Hospital Network Antwerp Middelheim and Hoge Beuken; the Brain and Emotion Laboratory, Department of Psychiatry (M.V.), SWITCH Laboratory, VIB (G.D.B., F.R.), and Laboratory for Cognitive Neurology, Department of Neurology (R.V.), University of Leuven; the Department of Neurology (M.V., R.V.), University Hospitals Leuven, Gasthuisberg; and the Department of Neurology (P.D.J., P.C.), Antwerp University Hospital, Edegem, Belgium. P.P.D.D. is also affiliated with the Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, the Netherlands.
Rik VandenbergheFrom the Department of Molecular Genetics (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., M.C., C.V.B.), VIB, Antwerp; Institute Born-Bunge (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., S.E., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., P.C., P.P.D.D., J.-J.M., M.C., C.V.B.), University of Antwerp; the Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; the Department of Neurology and Memory Clinic (S.E., P.P.D.D.), Hospital Network Antwerp Middelheim and Hoge Beuken; the Brain and Emotion Laboratory, Department of Psychiatry (M.V.), SWITCH Laboratory, VIB (G.D.B., F.R.), and Laboratory for Cognitive Neurology, Department of Neurology (R.V.), University of Leuven; the Department of Neurology (M.V., R.V.), University Hospitals Leuven, Gasthuisberg; and the Department of Neurology (P.D.J., P.C.), Antwerp University Hospital, Edegem, Belgium. P.P.D.D. is also affiliated with the Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, the Netherlands.
Peter De JongheFrom the Department of Molecular Genetics (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., M.C., C.V.B.), VIB, Antwerp; Institute Born-Bunge (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., S.E., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., P.C., P.P.D.D., J.-J.M., M.C., C.V.B.), University of Antwerp; the Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; the Department of Neurology and Memory Clinic (S.E., P.P.D.D.), Hospital Network Antwerp Middelheim and Hoge Beuken; the Brain and Emotion Laboratory, Department of Psychiatry (M.V.), SWITCH Laboratory, VIB (G.D.B., F.R.), and Laboratory for Cognitive Neurology, Department of Neurology (R.V.), University of Leuven; the Department of Neurology (M.V., R.V.), University Hospitals Leuven, Gasthuisberg; and the Department of Neurology (P.D.J., P.C.), Antwerp University Hospital, Edegem, Belgium. P.P.D.D. is also affiliated with the Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, the Netherlands.
Patrick CrasFrom the Department of Molecular Genetics (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., M.C., C.V.B.), VIB, Antwerp; Institute Born-Bunge (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., S.E., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., P.C., P.P.D.D., J.-J.M., M.C., C.V.B.), University of Antwerp; the Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; the Department of Neurology and Memory Clinic (S.E., P.P.D.D.), Hospital Network Antwerp Middelheim and Hoge Beuken; the Brain and Emotion Laboratory, Department of Psychiatry (M.V.), SWITCH Laboratory, VIB (G.D.B., F.R.), and Laboratory for Cognitive Neurology, Department of Neurology (R.V.), University of Leuven; the Department of Neurology (M.V., R.V.), University Hospitals Leuven, Gasthuisberg; and the Department of Neurology (P.D.J., P.C.), Antwerp University Hospital, Edegem, Belgium. P.P.D.D. is also affiliated with the Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, the Netherlands.
Peter P De DeynFrom the Department of Molecular Genetics (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., M.C., C.V.B.), VIB, Antwerp; Institute Born-Bunge (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., S.E., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., P.C., P.P.D.D., J.-J.M., M.C., C.V.B.), University of Antwerp; the Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; the Department of Neurology and Memory Clinic (S.E., P.P.D.D.), Hospital Network Antwerp Middelheim and Hoge Beuken; the Brain and Emotion Laboratory, Department of Psychiatry (M.V.), SWITCH Laboratory, VIB (G.D.B., F.R.), and Laboratory for Cognitive Neurology, Department of Neurology (R.V.), University of Leuven; the Department of Neurology (M.V., R.V.), University Hospitals Leuven, Gasthuisberg; and the Department of Neurology (P.D.J., P.C.), Antwerp University Hospital, Edegem, Belgium. P.P.D.D. is also affiliated with the Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, the Netherlands.
Jean-Jacques MartinFrom the Department of Molecular Genetics (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., M.C., C.V.B.), VIB, Antwerp; Institute Born-Bunge (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., S.E., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., P.C., P.P.D.D., J.-J.M., M.C., C.V.B.), University of Antwerp; the Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; the Department of Neurology and Memory Clinic (S.E., P.P.D.D.), Hospital Network Antwerp Middelheim and Hoge Beuken; the Brain and Emotion Laboratory, Department of Psychiatry (M.V.), SWITCH Laboratory, VIB (G.D.B., F.R.), and Laboratory for Cognitive Neurology, Department of Neurology (R.V.), University of Leuven; the Department of Neurology (M.V., R.V.), University Hospitals Leuven, Gasthuisberg; and the Department of Neurology (P.D.J., P.C.), Antwerp University Hospital, Edegem, Belgium. P.P.D.D. is also affiliated with the Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, the Netherlands.
Marc CrutsFrom the Department of Molecular Genetics (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., M.C., C.V.B.), VIB, Antwerp; Institute Born-Bunge (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., S.E., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., P.C., P.P.D.D., J.-J.M., M.C., C.V.B.), University of Antwerp; the Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; the Department of Neurology and Memory Clinic (S.E., P.P.D.D.), Hospital Network Antwerp Middelheim and Hoge Beuken; the Brain and Emotion Laboratory, Department of Psychiatry (M.V.), SWITCH Laboratory, VIB (G.D.B., F.R.), and Laboratory for Cognitive Neurology, Department of Neurology (R.V.), University of Leuven; the Department of Neurology (M.V., R.V.), University Hospitals Leuven, Gasthuisberg; and the Department of Neurology (P.D.J., P.C.), Antwerp University Hospital, Edegem, Belgium. P.P.D.D. is also affiliated with the Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, the Netherlands. christine.vanbroeckhoven@molgen.vib-ua.be marc.cruts@molgen.vib-ua.be.
Christine Van BroeckhovenFrom the Department of Molecular Genetics (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., M.C., C.V.B.), VIB, Antwerp; Institute Born-Bunge (I.G., S.V.M., J.v.d.Z., A.S., S.P., B.H., S.E., V.B., I.C., M.V.d.B., K.P., M.M., P.D.J., P.C., P.P.D.D., J.-J.M., M.C., C.V.B.), University of Antwerp; the Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; the Department of Neurology and Memory Clinic (S.E., P.P.D.D.), Hospital Network Antwerp Middelheim and Hoge Beuken; the Brain and Emotion Laboratory, Department of Psychiatry (M.V.), SWITCH Laboratory, VIB (G.D.B., F.R.), and Laboratory for Cognitive Neurology, Department of Neurology (R.V.), University of Leuven; the Department of Neurology (M.V., R.V.), University Hospitals Leuven, Gasthuisberg; and the Department of Neurology (P.D.J., P.C.), Antwerp University Hospital, Edegem, Belgium. P.P.D.D. is also affiliated with the Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, the Netherlands. christine.vanbroeckhoven@molgen.vib-ua.be marc.cruts@molgen.vib-ua.be.
BELNEU Consortium
VIB-KU Leuven Center for Brain & Disease Research · BEZNA Middelheim Hospital · BEGhent University Hospital · BEKU Leuven · BEVIB-UAntwerp Center for Molecular Neurology · BEUniversity of Antwerp · BE
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo assess the genetic contribution of TBK1, a gene implicated in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and FTD-ALS, in Belgian FTD and ALS patient cohorts containing a significant part of genetically unresolved patients.
methodsWe sequenced TBK1 in a hospital-based cohort of 482 unrelated patients with FTD and FTD-ALS and 147 patients with ALS and an extended Belgian FTD-ALS family DR158. We followed up mutation carriers by segregation studies, transcript and protein expression analysis, and immunohistochemistry.
resultsWe identified 11 patients carrying a loss-of-function (LOF) mutation resulting in an overall mutation frequency of 1.7% (11/629), 1.1% in patients with FTD (5/460), 3.4% in patients with ALS (5/147), and 4.5% in patients with FTD-ALS (1/22). We found 1 LOF mutation, p.Glu643del, in 6 unrelated patients segregating with disease in family DR158. Of 2 mutation carriers, brain and spinal cord was characterized by TDP-43-positive pathology. The LOF mutations including the p.Glu643del mutation led to loss of transcript or protein in blood and brain.
conclusionsTBK1 LOF mutations are the third most frequent cause of clinical FTD in the Belgian clinically based patient cohort, after C9orf72 and GRN, and the second most common cause of clinical ALS after C9orf72. These findings reinforce that FTD and ALS belong to the same disease continuum.
Indexed as
AdultAgedAged, 80 and overBelgiumCohort StudiesFemaleFrontotemporal DementiaHumansMaleMiddle AgedMutationPedigreeProtein Serine-Threonine KinasesProtein Serine-Threonine KinasesTBK1 protein, human
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.