TY - JOUR
T1 - Advances in understanding the molecular basis of frontotemporal dementia
AU - Rademakers, Rosa
AU - Neumann, Manuela
AU - MacKenzie, Ian R.
N1 - Funding Information:
R. Rademakers is funded by NIH grants P50 AG016574, R01 NS065782 and R01 AG026251, the ALS Therapy Alliance and the Consortium for Frontotemporal Dementia. M. Neumann is funded by the Swiss National Science Foundation grants 31003A-132864 and CRSII3 136222, the German Federal Ministry of Education and Research grant 01GI1005B, the Stavros–Niarchos Foundation, the Synapsis Foundation, and the Hans and Ilse Breuer Foundation. I. Mackenzie is funded by the Canadian Institutes of Health Research grants 179009 and 74580 and the Pacific Alzheimer’s Research Foundation Center grant C06-01.
PY - 2012/8
Y1 - 2012/8
N2 - Frontotemporal dementia (FTD) is a clinical syndrome with a heterogeneous molecular basis. Until recently, the underlying cause was known in only a minority of cases that were associated with abnormalities of the tau protein or gene. In 2006, however, mutations in the progranulin gene were discovered as another important cause of familial FTD. That same year, TAR DNA-binding protein 43 (TDP-43) was identified as the pathological protein in the most common subtypes of FTD and amyotrophic lateral sclerosis (ALS). Since then, substantial efforts have been made to understand the functions and regulation of progranulin and TDP-43, as well as their roles in neurodegeneration. More recently, other DNA/RNA binding proteins (FET family proteins) have been identified as the pathological proteins in most of the remaining cases of FTD. In 2011, abnormal expansion of a hexanucleotide repeat in the gene C9orf72 was found to be the most common genetic cause of both FTD and ALS. All common FTD-causing genes have seemingly now been discovered and the main pathological proteins identified. In this Review, we highlight recent advances in understanding the molecular aspects of FTD, which will provide the basis for improved patient care through the development of more-targeted diagnostic tests and therapies.
AB - Frontotemporal dementia (FTD) is a clinical syndrome with a heterogeneous molecular basis. Until recently, the underlying cause was known in only a minority of cases that were associated with abnormalities of the tau protein or gene. In 2006, however, mutations in the progranulin gene were discovered as another important cause of familial FTD. That same year, TAR DNA-binding protein 43 (TDP-43) was identified as the pathological protein in the most common subtypes of FTD and amyotrophic lateral sclerosis (ALS). Since then, substantial efforts have been made to understand the functions and regulation of progranulin and TDP-43, as well as their roles in neurodegeneration. More recently, other DNA/RNA binding proteins (FET family proteins) have been identified as the pathological proteins in most of the remaining cases of FTD. In 2011, abnormal expansion of a hexanucleotide repeat in the gene C9orf72 was found to be the most common genetic cause of both FTD and ALS. All common FTD-causing genes have seemingly now been discovered and the main pathological proteins identified. In this Review, we highlight recent advances in understanding the molecular aspects of FTD, which will provide the basis for improved patient care through the development of more-targeted diagnostic tests and therapies.
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U2 - 10.1038/nrneurol.2012.117
DO - 10.1038/nrneurol.2012.117
M3 - Review article
C2 - 22732773
AN - SCOPUS:84864981763
SN - 1759-4758
VL - 8
SP - 423
EP - 434
JO - Nature Reviews Neurology
JF - Nature Reviews Neurology
IS - 8
ER -