Future molecular studies are needed to explore how each this website mechanism contributes to neurodegeneration and pathological TDP-43 aggregation. Moreover, evaluation of larger numbers of patients with FTD and ALS associated with the expanded GGGGCC hexanucleotide repeat in C9ORF72 is warranted to further delineate the range of phenotypes and prevalence of these disorders, and to investigate the potential of the repeat for

properties such as anticipation and spontaneous mutation. Finally, we suggest that in future publications this genetic defect be referred to as “c9FTD/ALS. While our manuscript was in preparation we learned of another group who independently

identified repeat expansions in C9ORF72 as the cause of FTD and ALS linked to chromosome 9p ( Renton et al. 2011). Four extensive FTD and ALS patient cohorts and one control cohort were included in this study. All individuals agreed to be in the study and biological samples were obtained after informed consent from subjects and/or their proxies. Demographic and clinical information Pazopanib mw for each cohort is summarized in Table S1. The proband of chromosome 9p-linked family VSM-20 is part of a series of 26 probands ascertained at UBC, Vancouver, Canada, characterized by a pathological diagnosis of FTLD with TDP-43 pathology (FTLD-TDP) and a positive family history of FTD and/or ALS (UBC FTLD-TDP cohort). Clinical and pathological evaluations of VSM-20

were conducted at UCSF, UBC, and the Mayo Clinic ( Boxer et al., 2011). A second cohort of 93 pathologically confirmed FTLD-TDP patients independent of family history was selected from the Mayo Clinic Florida (MCF) brain bank (MCF FTLD-TDP cohort) which focuses predominantly on dementia. The clinical FTD cohort (MC Clinical FTD cohort) represents a sequential series of patients seen by the Behavioral Neurology sections at MCF (n = 197) and MCR (n = 177), the majority of whom were participants in the Mayo Alzheimer’s Disease Research Center. Members of Family 118 were participants in the Mayo Alzheimer’s Disease Patient Registry. Clinical FTD patients underwent a full these neurological evaluation, and all who were testable had a neuropsychological evaluation. Structural neuroimaging was performed in all patients and functional imaging was performed in many patients. Patients with a clinical diagnosis of behavioral variant FTD (bvFTD), semantic dementia or progressive non-fluent aphasia based on Neary criteria ( Neary et al., 1998), or patients with the combined phenotype of bvFTD and ALS were included in this study, while patients with a diagnosis of logopenic aphasia or corticobasal syndrome were excluded.