CBD gene expression data were compared with whole blood and lung tissue in sarcoidosis from the Gene Expression Omnibus.We confirmed almost 450 genes that were significantly differentially expressed between CBD and controls.
In order to determine the frequency of microtubule-associated protein tau gene (MAPT) mutations and rare variants in CBD, we performed a systematic sequence analysis of MAPT coding and 3′ untranslated region (3′UTR) in a large cohort of autopsy-confirmed CBD patients (N = 109).
We hypothesized that intermediate C9orf72 repeats are a genetic risk factor for corticobasal degeneration (CBD), a neurodegenerative disease that can be clinically similar to Parkinson's but has distinct tau protein pathology.
Common and rare variants in the MAPT gene increase the risk for sporadic FTLD-Tau, including progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD).
Pathogenic mutations in the tau gene (microtubule associated protein tau, MAPT) are linked to the onset of tauopathy, but the A152T variant is unique in acting as a risk factor for a range of disorders including Alzheimer's disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and dementia with Lewy bodies (DLB).
Intracellular tau protein aggregates are a pathological hallmark of neurodegenerative tauopathies, including Alzheimer disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick disease.
In conclusion, the present study indicates that CBD with severe TDP-43 pathology is a distinct clinicopathologic subtype of CBD, characterized by PSP-like clinical presentations, severe tau pathology in the olivopontocerebellar system, and low frequency of MAPT H1 haplotype.
Microtubule-associated protein tau (MAPT) gene is compelling among the susceptibility genes of neurodegenerative diseases which include Alzheimer's disease (AD), Parkinson's disease (PD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS).
Our findings suggest: (1) novel genetic overlap between CBD and PSP beyond the MAPT locus; (2) strong ties between CBD and FTD through the MAPT clade, and (3) unique combinations of overlapping genes that may, in part, influence selective regional or neuronal vulnerability observed in specific tauopathies.
Neurodegenerative conditions, including progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and frontotemporal dementia (FTD), are primarily characterized by accumulation of tau protein in the brain.
We calculated CBD prevalences from allele-specific DNA sequences of 853 workers for Human Leukocyte Antigen (HLA)-DPB1 genotypes and groups characterized by number of E69-containing alleles and by calculated surface electronegativity of HLA-DPB1.
We identify new CBD susceptibility loci and show that CBD and PSP share a genetic risk factor other than MAPT at 3p22 MOBP (myelin-associated oligodendrocyte basic protein).
Multiple epidemiologic studies demonstrate associations between chronic beryllium disease (CBD), beryllium sensitization (BeS), and HLA-DPB1 alleles with a glutamic acid residue at position 69 (E69).
However, in the sporadic tauopathies such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) where MAPT mutation is absent, common variation in MAPT that defines the H1 and H2 haplotype clades strongly influences disease risk.
Because inbred strains of mice have not provided good models of CBD to date, three strains of HLA-DPB1 transgenic mice in an FVB/N background were developed; each contains a single allele of HLA-DPB1 that confers a different magnitude of risk for chronic beryllium disease: HLA-DPB1*0401 (OR approximately 0.2), HLA-DPB1*0201 (OR approximately 3), and HLA-DPB1*1701 (OR approximately 46).
In addition, the MAPT H1-clade specific sub-haplotype, H1c, has been strongly associated with the tauopathies, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) and, to a lesser extent, with Alzheimer's disease (AD).
Recent studies have detected an over-representation of the H1 haplotype of the MAPT gene in neurodegenerative disorders such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), frontotemporal dementia (FTD) and Parkinson's disease (PD), whereas the H2 haplotype has been found to be related to familial FTD.
Previously we have shown that the H1c haplotype on the background of the H1 clade of haplotypes at the MAPT locus is associated with increased risk for progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and Alzheimer's disease (AD).
In conclusion, both DRB1*13 and rs3117099TT homozygosity are associated with CBD in *Glu69-negative subjects, while DPB1*Glu69 is associated with CBD and BeS compared with Be-exp.