title: The genetics of frontotemporal lobar degeneration.
abstract: The clinical disorders associated with frontotemporal lobar degeneration (FTLD) are increasingly recognized as an important cause of early-onset dementia. Patients usually present with progressive changes in personality, behavior, or language, progressing to general cognitive impairment and ultimately death. In the past decade, improved clinical and histopathologic characterization uncovered extensive heterogeneity, and multiple clinical and pathologic FTLD subtypes were defined. Simultaneously, the discovery of four causal FTLD genes emphasized the genetic complexity associated with FTLD. More recently, the field of FTLD has gained increased attention as a result of two major findings. First, mutations in the progranulin gene (PGRN) were recognized as a major cause of FTLD with ubiquitin-positive and tau-negative inclusions (FTLD-U), and subsequently the TAR DNA-binding protein-43 (TDP-43) was identified as a key protein within the ubiquitinated inclusions in FTLD-U and amyotrophic lateral sclerosis (ALS). In this report, we outline the progress made in the study of the genetic etiologies and neuropathologic substrates in FTLD.
authors.affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, FL 32224, USA. rademakers.rosa@mayo.edu
authors.forename: Rosa
authors.initials: R
authors.lastname: Rademakers
authors.forename: Mike
authors.initials: M
authors.lastname: Hutton
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D018797:Cell Cycle Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D003704:Dementia / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D056827:Endosomal Sorting Complexes Required for Transport; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D000077153:Progranulins; D000074405:Valosin Containing Protein
chemical_list: C503812:CHMP2B protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D000077153:Progranulins; D000251:Adenosine Triphosphatases; D000074405:Valosin Containing Protein