Update on recent molecular and genetic advances in frontotemporal lobar degeneration.
Great strides have been made in the last 2 years in the field of frontotemporal lobar degeneration (FTLD), particularly with respect to the genetics and molecular biology of FTLD with ubiquitinated inclusions. It is now clear that most cases of familial FTLD with ubiquitinated inclusions have mutations in the progranulin gene, located on chromosome 17. It is also clear that most ubiquitinated inclusions in FTLD with ubiquitinated inclusions are composed primarily of TAR DNA-binding protein-43. Thus, FTLDs can be separated into 2 major groups (i.e. tauopathies and ubiquitinopathies), and most of the ubiquitinopathies can now be defined as TAR DNA-binding protein-43 proteinopathies. Many of the familial FTLDs are linked to chromosome 17, including both the familial tauopathies and the familial TAR DNA-binding protein-43 proteinopathies with progranulin mutations. This review highlights the neuropathologic features and the most important discoveries of the last 2 years and places these findings into the historical context of FTLD.
Bigio
Eileen H
EH
Department of Pathology, Cognitive Neurology and Alzheimer Disease Center, Northwestern University Feinberg School of Medicine, 710 N. Fairbanks Court, Chicago, IL 60611, USA. e-bigio@northwestern.edu
D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D003704:Dementia / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D009154:Mutation; D000077153:Progranulins; D024801:Tauopathies; D054875:Ubiquitination
D004268:DNA-Binding Proteins; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins