Ghent University Academic Bibliography

Advanced

The genetics and neuropathology of frontotemporal lobar degeneration

ANNE SIEBEN UGent, Tim Van Langenhove, Sebastiaan Engelborghs, Jean-Jacques Martin, Paul Boon UGent, Patrick Cras, Peter-Paul De Deyn, Patrick Santens UGent, Christine Van Broeckhoven and Marc Cruts (2012) ACTA NEUROPATHOLOGICA. 124(3). p.353-372
abstract
Frontotemporal lobar degeneration (FTLD) is a heterogeneous group of disorders characterized by disturbances of behavior and personality and different types of language impairment with or without concomitant features of motor neuron disease or parkinsonism. FTLD is characterized by atrophy of the frontal and anterior temporal brain lobes. Detailed neuropathological studies have elicited proteinopathies defined by inclusions of hyperphosphorylated microtubule-associated protein tau, TAR DNA-binding protein TDP-43, fused-in-sarcoma or yet unidentified proteins in affected brain regions. Rather than the type of proteinopathy, the site of neurodegeneration correlates relatively well with the clinical presentation of FTLD. Molecular genetic studies identified five disease genes, of which the gene encoding the tau protein (MAPT), the growth factor precursor gene granulin (GRN), and C9orf72 with unknown function are most frequently mutated. Rare mutations were also identified in the genes encoding valosin-containing protein (VCP) and charged multivesicular body protein 2B (CHMP2B). These genes are good markers to distinguish underlying neuropathological phenotypes. Due to the complex landscape of FTLD diseases, combined characterization of clinical, imaging, biological and genetic biomarkers is essential to establish a detailed diagnosis. Although major progress has been made in FTLD research in recent years, further studies are needed to completely map out and correlate the clinical, pathological and genetic entities, and to understand the underlying disease mechanisms. In this review, we summarize the current state of the rapidly progressing field of genetic, neuropathological and clinical research of this intriguing condition.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (review)
publication status
published
subject
keyword
VALOSIN-CONTAINING-PROTEIN, MOTOR-NEURON DISEASE, PROGRESSIVE SUPRANUCLEAR PALSY, AMYOTROPHIC-LATERAL-SCLEROSIS, FUS, TDP-43, Tau, CHMP2B, VCP, C9orf72, GRN, MAPT, Frontotemporal lobar degeneration, Proteinopathy, HEXANUCLEOTIDE REPEAT EXPANSION, INCLUSION-BODY MYOPATHY, ARGYROPHILIC GRAIN DISEASE, TAU-NEGATIVE INCLUSIONS, GENOME-WIDE ASSOCIATION, NUCLEAR FACTOR TDP-43
journal title
ACTA NEUROPATHOLOGICA
Acta Neuropathol.
volume
124
issue
3
pages
353 - 372
Web of Science type
Review
Web of Science id
000307757200005
JCR category
PATHOLOGY
JCR impact factor
9.734 (2012)
JCR rank
2/77 (2012)
JCR quartile
1 (2012)
ISSN
0001-6322
DOI
10.1007/s00401-012-1029-x
language
English
UGent publication?
yes
classification
A1
copyright statement
I have retained and own the full copyright for this publication
id
3024998
handle
http://hdl.handle.net/1854/LU-3024998
date created
2012-10-11 15:32:20
date last changed
2013-01-23 10:37:08
@article{3024998,
  abstract     = {Frontotemporal lobar degeneration (FTLD) is a heterogeneous group of disorders characterized by disturbances of behavior and personality and different types of language impairment with or without concomitant features of motor neuron disease or parkinsonism. FTLD is characterized by atrophy of the frontal and anterior temporal brain lobes. Detailed neuropathological studies have elicited proteinopathies defined by inclusions of hyperphosphorylated microtubule-associated protein tau, TAR DNA-binding protein TDP-43, fused-in-sarcoma or yet unidentified proteins in affected brain regions. Rather than the type of proteinopathy, the site of neurodegeneration correlates relatively well with the clinical presentation of FTLD. Molecular genetic studies identified five disease genes, of which the gene encoding the tau protein (MAPT), the growth factor precursor gene granulin (GRN), and C9orf72 with unknown function are most frequently mutated. Rare mutations were also identified in the genes encoding valosin-containing protein (VCP) and charged multivesicular body protein 2B (CHMP2B). These genes are good markers to distinguish underlying neuropathological phenotypes. Due to the complex landscape of FTLD diseases, combined characterization of clinical, imaging, biological and genetic biomarkers is essential to establish a detailed diagnosis. Although major progress has been made in FTLD research in recent years, further studies are needed to completely map out and correlate the clinical, pathological and genetic entities, and to understand the underlying disease mechanisms. In this review, we summarize the current state of the rapidly progressing field of genetic, neuropathological and clinical research of this intriguing condition.},
  author       = {SIEBEN, ANNE and Van Langenhove, Tim and Engelborghs, Sebastiaan and Martin, Jean-Jacques and Boon, Paul and Cras, Patrick and De Deyn, Peter-Paul and Santens, Patrick and Van Broeckhoven, Christine and Cruts, Marc},
  issn         = {0001-6322},
  journal      = {ACTA NEUROPATHOLOGICA},
  keyword      = {VALOSIN-CONTAINING-PROTEIN,MOTOR-NEURON DISEASE,PROGRESSIVE SUPRANUCLEAR PALSY,AMYOTROPHIC-LATERAL-SCLEROSIS,FUS,TDP-43,Tau,CHMP2B,VCP,C9orf72,GRN,MAPT,Frontotemporal lobar degeneration,Proteinopathy,HEXANUCLEOTIDE REPEAT EXPANSION,INCLUSION-BODY MYOPATHY,ARGYROPHILIC GRAIN DISEASE,TAU-NEGATIVE INCLUSIONS,GENOME-WIDE ASSOCIATION,NUCLEAR FACTOR TDP-43},
  language     = {eng},
  number       = {3},
  pages        = {353--372},
  title        = {The genetics and neuropathology of frontotemporal lobar degeneration},
  url          = {http://dx.doi.org/10.1007/s00401-012-1029-x},
  volume       = {124},
  year         = {2012},
}

Chicago
SIEBEN, ANNE, Tim Van Langenhove, Sebastiaan Engelborghs, Jean-Jacques Martin, Paul Boon, Patrick Cras, Peter-Paul De Deyn, Patrick Santens, Christine Van Broeckhoven, and Marc Cruts. 2012. “The Genetics and Neuropathology of Frontotemporal Lobar Degeneration.” Acta Neuropathologica 124 (3): 353–372.
APA
SIEBEN, A., Van Langenhove, T., Engelborghs, S., Martin, J.-J., Boon, P., Cras, P., De Deyn, P.-P., et al. (2012). The genetics and neuropathology of frontotemporal lobar degeneration. ACTA NEUROPATHOLOGICA, 124(3), 353–372.
Vancouver
1.
SIEBEN A, Van Langenhove T, Engelborghs S, Martin J-J, Boon P, Cras P, et al. The genetics and neuropathology of frontotemporal lobar degeneration. ACTA NEUROPATHOLOGICA. 2012;124(3):353–72.
MLA
SIEBEN, ANNE, Tim Van Langenhove, Sebastiaan Engelborghs, et al. “The Genetics and Neuropathology of Frontotemporal Lobar Degeneration.” ACTA NEUROPATHOLOGICA 124.3 (2012): 353–372. Print.