Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy
Open accessAbstract
Corticobasal degeneration (CBD) is a neurodegenerative disorder affecting movement and cognition, definitively diagnosed only at autopsy. Here, we conduct a genome-wide association study (GWAS) in CBD cases (n=152) and 3,311 controls, and 67 CBD cases and 439 controls in a replication stage. Associations with meta-analysis were 17q21 at MAPT (P=1.42 × 10−12), 8p12 at lnc-KIF13B-1, a long non-coding RNA (rs643472; P=3.41 × 10−8), and 2p22 at SOS1 (rs963731; P=1.76 × 10−7). Testing for association of CBD with top progressive supranuclear palsy (PSP) GWAS single-nucleotide polymorphisms (SNPs) identified associations at MOBP (3p22; rs1768208; P=2.07 × 10−7) and MAPT H1c (17q21; rs242557; P=7.91 × 10−6). We previously reported SNP/transcript level associations with rs8070723/MAPT, rs242557/MAPT, and rs1768208/MOBP and herein identified association with rs963731/SOS1. 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).
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Written from the paper’s full text.
TL;DR
This first corticobasal degeneration (CBD) GWAS in autopsy-proven cases identified genome-wide significant associations at MAPT and lnc-KIF13B-1, plus suggestive loci at SOS1 and MOBP. It reports that CBD and progressive supranuclear palsy (PSP) share a non-MAPT genetic risk factor at 3p22 MOBP.
Key findings
- Meta-analysis found associations at MAPT (rs393152, P=1.42 × 10−12), lnc-KIF13B-1 at 8p12 (rs643472, P=3.41 × 10−8), SOS1 at 2p22 (rs963731, P=1.76 × 10−7), MOBP at 3p22 (rs1768208, P=2.07 × 10−7), and MAPT H1c (rs242557, P=7.91 × 10−6).
- Discovery-stage conditional logistic regression showed MAPT rs393152 OR=3.45, P=6.71 × 10−9; lnc-KIF13B-1 rs643472 OR=1.88, P=7.12 × 10−7; SOS1 rs963731 OR=2.46, P=2.04 × 10−6; MOBP rs1768208 OR=1.65, P=3.86 × 10−5; and MAPT H1c rs242557 OR=1.48, P=1.20 × 10−3.
- The MOBP association was stronger in CBD than in PSP: MAFCBD=0.40, OR=1.71 versus MAFPSP=0.36, OR=1.39, making it the first reported non-MAPT shared genetic risk factor between CBD and PSP.
- eQTL analysis detected SOS1/rs963731 associations with transcript levels in cerebellum (P=4.61 × 10−4) and temporal cortex (P=2.80 × 10−6); previously reported MAPT/rs8070723 and MOBP/rs1768208 SNP/transcript associations were also noted.
Methods
- Two-stage GWAS: discovery stage included 152 autopsy-proven CBD cases and 3,311 controls; replication stage included 67 autopsy-proven CBD cases and 457 controls (the abstract states 439 controls). Discovery genotyping used Human 660W-Quad and Human HapMap550 Infinium BeadChips; replication used Taqman assays or Sanger sequencing.
- Association testing used conditional logistic regression under an additive model with the first multidimensional scaling principal component as a covariate; discovery and replication results were combined by random-effects meta-analysis. Genotype imputation used the 1,000 Genomes European reference, and eQTL analysis used a brain expression GWAS of cerebellar and temporal cortex samples.
- Additional analyses included HaploRegv2 annotation, testing of top PSP GWAS SNPs, and quantitative PCR for lnc-KIF13B-1 expression in superior frontal cortex from CBD cases and controls.
Limitations
- The paper states that the sample size is a clear limitation, that a stringent discovery threshold (P<10−5) was used to control false positives, that power was low to detect modest-effect variants, and that two associations did not replicate.
- Evident from the text: the replication cohort was small (67 CBD cases), and the control count differs between the abstract (439) and the results/methods (457). Also, eQTL analysis could not be performed for the 8p12 locus because the eGWAS lacked rs643472 or LD proxies and DUSP4 expression probes failed quality control.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Cites
Statistics
Claims the paper makes
3 of 14 cited sources checked · 1 supported · 0 flagged · accuracy not yet measured
- Premisecitation
Fewer than 50% of patients with corticobasal syndrome have CBD at autopsy.
“This phenotypic variability results in <50% of patients with CBS having CBD at autopsy567.”
Quote in the paperSubstantial claim1 of 3 sources checked- cites [5] Kouri, N., Whitwell, J. L., Josephs, K. A., Rademakers, R. & Dickson, D. W. Corticobasal degeneration: a pathologically distinct 4R tauopathy. Nat. Rev. Neurol. 7, 263–272 (2011). source
The Introduction says autopsy studies show considerable variation in the pathology of patients with CBS, supporting the point that CBS does not always indicate CBD. The Corticobasal syndrome section gives approximately 50% for the reverse group—autopsy-confirmed CBD cases presenting with CBS—not the percentage of CBS patients who have CBD at autopsy. Our copy therefore does not establish the claimed <50% figure. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites [6] Ling, H. et al. Does corticobasal degeneration exist? A clinicopathological re-evaluation. Brain 133, 2045–2057 (2010). source
- cites [7] Boeve, B. F. et al. Pathologic heterogeneity in clinically diagnosed corticobasal degeneration. Neurology 53, 795–800 (1999). source
- Findingcitation
CBD cases have a greater OR estimate at MOBP compared with PSP (MAFCBD=0.40; OR=1.71; MAFPSP=0.36; OR=1.39).
“In support of the MOBP locus being a shared genetic risk factor between CBD and PSP, CBD cases have an even greater OR estimate compared with PSP (MAFCBD=0.40; OR=1.71; MAFPSP=0.36; OR=1.39; ref. 17).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [17] Hoglinger, G. U. et al. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nat. Genet. 43, 699–705 (2011). source
The paper’s Abstract reports a significant association between MOBP and PSP risk. Our copy does not report MOBP results for CBD or the cited allele frequencies and odds ratios, so it does not support the claimed CBD–PSP comparison (searched: CBD, corticobasal degeneration, and the stated estimates). (LLM, conf=0.83)
Experimental — accuracy not yet measured
- Findingown data
Random effects meta-analysis showed suggestive evidence for association at the MAPT H1c haplotype (rs242557, Pmeta=7.9 × 10−6).
“SNPs at MOBP (rs1768208, Pmeta=2.1 × 10−7) (Fig. 1c), SOS1 (rs963731, Pmeta=1.8 × 10−7) (Fig. 1d) and MAPT H1c haplotype (rs242557, Pmeta=7.9 × 10−6) had suggestive evidence for association with CBD.”
- Also stated in: § Discussion · plain
“In addition, CBD was also associated with rs242557 (P=7.91 × 10−6), a SNP tagging the H1c subhaplotype at 17q21, shown to be associated with PSP and located in a regulatory region influencing MAPT expression26.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
rs963731 at 2p22 alters 18 regulatory motifs.
“Results show that rs643472 is located in an enhancer region in multiple cell lines and alters three transcription factor motifs, rs963731 at 2p22 alters 18 regulatory motifs, and rs1768208 at 3p22 is in high LD (R2=0.89–0.98) with five SNPs that are located in enhancer regions in several brain regions (Supplementary Table 6 and Supplementary Fig. 5).”
Quote in the paperNot a substantial claim - Findingown data
rs242557 at the MAPT locus was associated with CBD (OR=1.48, P=1.20 × 10−3).
“Testing for association using conditional logistic regression analysis with the top PSP GWAS SNPs identified rs1768208 (OR=1.65, P=3.86 × 10−5), an intronic SNP in MOBP (myelin-associated oligodendrocyte basic protein), and rs242557 (OR=1.48, P=1.20 × 10−3) at the MAPT locus to be associated with CBD.”
Quote in the paperSubstantial claim
- Findingown data
Testing top PSP GWAS SNPs identified rs1768208 in MOBP as associated with CBD (OR=1.65, P=3.86 × 10−5).
“Testing for association using conditional logistic regression analysis with the top PSP GWAS SNPs identified rs1768208 (OR=1.65, P=3.86 × 10−5), an intronic SNP in MOBP (myelin-associated oligodendrocyte basic protein), and rs242557 (OR=1.48, P=1.20 × 10−3) at the MAPT locus to be associated with CBD.”
Quote in the paperSubstantial claim - Findingown data
The top SNP at EIF2AK3 (rs7571971) did not show an association with CBD (P=0.057; OR=1.27).
“The top SNP at EIF2AK3 (rs7571971) did not show an association with CBD (P=0.057; OR=1.27), but the OR was of similar effect size as observed for PSP (Supplementary Table 3).”
Quote in the paperNot a substantial claim - Findingown data
Random effects meta-analysis showed suggestive evidence for association at MOBP (rs1768208, Pmeta=2.1 × 10−7).
“SNPs at MOBP (rs1768208, Pmeta=2.1 × 10−7) (Fig. 1c), SOS1 (rs963731, Pmeta=1.8 × 10−7) (Fig. 1d) and MAPT H1c haplotype (rs242557, Pmeta=7.9 × 10−6) had suggestive evidence for association with CBD.”
Quote in the paperSubstantial claim - Findingown data
Including the number of H1 alleles as a covariate in the random effects meta-analysis lost the association for rs242557 (OR=1.18, Pmeta=0.11).
“Performing the same random effects meta-analysis while including the number of H1 alleles as a covariate, the association was lost (rs242557, OR=1.18, Pmeta=0.11).”
Quote in the paperSubstantial claim - Findingown data
Beta values for SNP/transcript associations showed increased expression levels with each copy of the risk allele.
“Beta values for SNP/transcript associations showed increased expression levels with each copy of the risk allele.”
Quote in the paperNot a substantial claim - Findingown data
Random effects meta-analysis showed a genome-wide significant association at lnc-KIF13B-1 (rs643472, Pmeta=3.4 × 10−8).
“Using PLINK to perform random effects meta-analysis, or the weighted average of the effect sizes of the discovery and replication stages, showed genome-wide significant associations at MAPT (rs393152, Pmeta=1.4 × 10−12) (Fig. 1a) and lnc-KIF13B-1 (rs643472, Pmeta=3.4 × 10−8; Table 2) (Fig. 1b).”
Quote in the paperSubstantial claim - Findingown data
eQTL analysis detected significant associations with SOS1/rs963731 (cerebellum P=4.61 × 10−4; temporal cortex P=2.80 × 10−6).
“We also detected significant associations with SOS1/rs963731 (cerebellum: P=4.61 × 10−4; temporal cortex: P=2.80 × 10−6) upon eQTL analysis (Table 4).”
Quote in the paperNot a substantial claim - Findingown data
Random effects meta-analysis showed a genome-wide significant association at MAPT (rs393152, Pmeta=1.4 × 10−12).
“Using PLINK to perform random effects meta-analysis, or the weighted average of the effect sizes of the discovery and replication stages, showed genome-wide significant associations at MAPT (rs393152, Pmeta=1.4 × 10−12) (Fig. 1a) and lnc-KIF13B-1 (rs643472, Pmeta=3.4 × 10−8; Table 2) (Fig. 1b).”
Quote in the paperSubstantial claim - Findingown data
The discovery stage found nominal evidence for association at rs963731 in SOS1 on chromosome 2q22 (OR=2.46, P=2.04 × 10−6).
“and rs963731 (OR=2.46, P=2.04 × 10−6), an intronic SNP in SOS1 on chromosome 2q22 (Supplementary Fig. 4).”
Quote in the paperNot a substantial claim - Findingown data
rs631312 was associated with CBD (OR=1.89, CI=1.30-2.75, P=8.77 × 10−4).
“Two of the five SNPs (rs631312 and rs1768190) were further genotyped in CBD (n=133) and controls (n=457), and association testing showed similar results with CBD (OR=1.89 (CI=1.30–2.75), P=8.77 × 10−4; OR=1.91 (CI=1.31–2.77), P=7.24 × 10−4, respectively) to rs1768208 (Table 3).”
Quote in the paperSubstantial claim - Findingown data
The random effects meta-analysis identified two associations that did not replicate.
“This proved to be a useful approach because the random effects meta-analysis identified two associations that did not replicate (Table 2).”
Quote in the paperSubstantial claim - Findingown data
rs1768190 was associated with CBD (OR=1.91, CI=1.31-2.77, P=7.24 × 10−4).
“Two of the five SNPs (rs631312 and rs1768190) were further genotyped in CBD (n=133) and controls (n=457), and association testing showed similar results with CBD (OR=1.89 (CI=1.30–2.75), P=8.77 × 10−4; OR=1.91 (CI=1.31–2.77), P=7.24 × 10−4, respectively) to rs1768208 (Table 3).”
Quote in the paperSubstantial claim - Findingown data
Testing for association of CBD with imputed genotypes did not improve association results.
“Testing for association of CBD with imputed genotypes did not improve association results.”
Quote in the paperNot a substantial claim - Findingown data
Random effects meta-analysis showed suggestive evidence for association at SOS1 (rs963731, Pmeta=1.8 × 10−7).
“SNPs at MOBP (rs1768208, Pmeta=2.1 × 10−7) (Fig. 1c), SOS1 (rs963731, Pmeta=1.8 × 10−7) (Fig. 1d) and MAPT H1c haplotype (rs242557, Pmeta=7.9 × 10−6) had suggestive evidence for association with CBD.”
Quote in the paperNot a substantial claim - Findingown data
rs1768208 at 3p22 is in high LD (R2=0.89-0.98) with five SNPs located in enhancer regions in several brain regions.
“Results show that rs643472 is located in an enhancer region in multiple cell lines and alters three transcription factor motifs, rs963731 at 2p22 alters 18 regulatory motifs, and rs1768208 at 3p22 is in high LD (R2=0.89–0.98) with five SNPs that are located in enhancer regions in several brain regions (Supplementary Table 6 and Supplementary Fig. 5).”
Quote in the paperNot a substantial claim - Findingown data
The discovery stage found nominal evidence for association at rs643472 in lnc-KIF13B-1 on chromosome 8p12 (OR=1.88, P=7.12 × 10−7).
“We also found nominal evidence for association testing using conditional logistic regression analysis at two novel susceptibility loci—rs643472 (OR=1.88, P=7.12 × 10−7), an intronic SNP in lnc-KIF13B-1 (TCONS_00014956, a large intergenic non-coding RNA, or lincRNA) located between KIF13B and DUSP4 on chromosome 8p12”
Quote in the paperNot a substantial claim - Findingown data
lnc-KIF13B-1 expression in superior frontal cortex of 22 CBD and 20 normal cases showed a statistical trend for greater expression with the minor risk allele.
“This identified a statistical trend for greater lnc-KIF13B-1 expression with the minor risk allele (Supplementary Fig. 6).”
Quote in the paperNot a substantial claim - Findingown data
The discovery GWAS identified a genome-wide significant association at 17q21.31 encompassing MAPT (rs393152, OR=3.45, P=6.71 × 10−9).
“The discovery stage identified one genome-wide significant association at 17q21.31, which encompasses MAPT (rs393152, odds ratio (OR)=3.45, P=6.71 × 10−9) testing using conditional logistic regression analysis (Fig. 1a; Table 2) and 12 SNPs in LD with rs393152 (Supplementary Table 2).”
Quote in the paperSubstantial claim - Interpretationown data
This is the first non-MAPT genetic risk factor shared between CBD and PSP.
“Importantly, this is the first non-MAPT genetic risk factor shared between CBD and PSP.”
Quote in the paperSubstantial claim - Study design and conductown data
Repeating the discovery-stage CBD GWAS with a different control data set (NGRC-PD, 1,986 controls) found similar association results.
“Furthermore, we repeated the discovery stage CBD GWAS with a different control data set, 1,986 controls from dbGaP data set NeuroGenetics Research Consortium (NGRC-PD; phs000196.v2.p1), analysed by logistic regression under an additive model and found similar association results (Supplementary Table 5).”
Quote in the paperNot a substantial claim - Interpretationreasoning
The novel susceptibility loci for CBD may link common genetic variation to aberrant tau phosphorylation.
“Taken together, the novel susceptibility loci for CBD may link common genetic variation to aberrant tau phosphorylation.”
Quote in the paperSubstantial claim - Study design and conductown data
The minor allele frequencies for the top SNPs in younger controls did not differ significantly from those of older controls (N=3,720) in three dbGaP data sets.
“The MAFs for the top SNPs in younger controls of this study did not differ significantly from those of older controls (N=3,720) in three data sets from the National Institute of Health Database for Genotypes and Phenotypes (dbGaP; http://www.ncbi.nlm.nih.gov/gap; Supplementary Table 4).”
Quote in the paperNot a substantial claim - Study design and conductown data
The first principal component as a covariate in logistic regression analyses was sufficient to correct for population substructure, based on a reduction of λ from 1.06 to 1.01.
“Quantile–quantile (QQ) plots and the genomic inflation factor (λ) show that the first principal component as a covariate in logistic regression analyses was sufficient to correct for population substructure based on a reduction of λ from the unadjusted (λ=1.06) to adjusted (λ=1.01; Supplementary Fig. 2).”
Quote in the paperSubstantial claim - Study design and conductreasoning
A stringent significance threshold (P<10−5) was applied in the discovery stage to select SNPs for genotyping in the replication stage.
“To control the false-positive rate due to the small sample size, a stringent significance threshold (P<10−5) was applied in the discovery stage to select SNPs for genotyping in the replication stage.”
Quote in the paperSubstantial claim - Interpretationown data
The first CBD GWAS identified MAPT and MOBP as shared genetic risk factors between CBD and PSP.
“In conclusion, this first CBD GWAS identified MAPT and MOBP as shared genetic risk factors between CBD and PSP.”
Quote in the paperSubstantial claim - Premisecitation
rs242557 is located in a regulatory region influencing MAPT expression.
“a SNP tagging the H1c subhaplotype at 17q21, shown to be associated with PSP and located in a regulatory region influencing MAPT expression26.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [26] Rademakers, R. et al. High-density SNP haplotyping suggests altered regulation of tau gene expression in progressive supranuclear palsy. Hum. Mol. Genet. 14, 3281–3292 (2005). source
- Study design and conductown data
The power analysis shows low power to detect genome-wide associations of variants with modest effect sizes.
“The disadvantage of applying stringent criteria is the possibility of false-negative associations, as evidenced from the power analysis, which show low power to detect genome-wide associations of variants with modest effect sizes (Supplementary Tables 8 and 9).”
Quote in the paperSubstantial claim- The authors state this as an assumption: Genotype frequencies are in Hardy–Weinberg equilibrium in CBD cases and control individuals separately, and association testing is performed using logistic regression under an additive model.
- Classified as probably not a substantial claim. 8
- May combine two claims. 8
Classified as probably not a substantial claim.
PremisecitationThe first PSP GWAS discovered three non-MAPT susceptibility loci at STX6, EIF2AK3, and MOBP.
“Recently, the first PSP GWAS17 discovered three non-MAPT susceptibility loci at STX6, EIF2AK3, and MOBP, raising the possibility that additional non-MAPT genetic risk factors or modifiers may also exist for CBD.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [17] Hoglinger, G. U. et al. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nat. Genet. 43, 699–705 (2011). source
May combine two claims.
Findingown dataHaploRegv2 results show that rs643472 is located in an enhancer region in multiple cell lines and alters three transcription factor motifs.
“Results show that rs643472 is located in an enhancer region in multiple cell lines and alters three transcription factor motifs, rs963731 at 2p22 alters 18 regulatory motifs, and rs1768208 at 3p22 is in high LD (R2=0.89–0.98) with five SNPs that are located in enhancer regions in several brain regions (Supplementary Table 6 and Supplementary Fig. 5).”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationCBD is a late-onset neurodegenerative disorder that can only be diagnosed upon neuropathologic examination.
“CBD is a late-onset neurodegenerative disorder that can only be diagnosed upon neuropathologic examination, which has impeded the ability to conduct genome-wide association studies (GWASs).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1] Dickson, D. W. et al. Office of rare diseases neuropathologic criteria for corticobasal degeneration. J. Neuropathol. Exp. Neurol. 61, 935–946 (2002). source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationCBD is a tauopathy with abnormal aggregates of microtubule-associated protein tau in the brain.
“Similar to progressive supranuclear palsy (PSP), Alzheimer’s disease (AD), and chronic traumatic encephalopathy, CBD is a tauopathy, having abnormal aggregates of microtubule-associated protein tau in the brain1.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [1] Dickson, D. W. et al. Office of rare diseases neuropathologic criteria for corticobasal degeneration. J. Neuropathol. Exp. Neurol. 61, 935–946 (2002). source
May combine two claims.
Interpretationown dataBoth CBD and PSP now have confirmed genome-wide significant associations at the MAPT locus.
“Both CBD and PSP now have confirmed genome-wide significant associations at the MAPT locus.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataThe mean RIN in frontal cortex for 22 CBD cases (5.6±0.38) was not different from 19 controls (6.4±0.77).
“The mean RIN in frontal cortex for 22 CBD cases (5.6±0.38) were not different from 19 controls (6.4±0.77).”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductreasoningDiscovery-stage controls were not age matched to cases, but were genotyped at the same center using the same protocol as the CBD cases.
“Discovery stage controls were recruited from the Children’s Hospital of Philadelphia Health Care Network, and although these controls are not age matched to the cases, the justification for using this cohort is that they were all genotyped at the same center using the same protocol as the CBD cases.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenOnly samples with an RNA integrity value >5 were included in the lnc-KIF13B-1 expression study.
“only samples with an RNA integrity value >5 were included in this study.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim. May combine two claims.
PremisecitationNeuropathologic diagnostic criteria for CBD require tau inclusions in neurons and glia, with tau astrocytic plaques, and extensive thread-like pathology in grey and white matter.
“Neuropathologic diagnostic criteria for CBD are based on tau immunohistochemistry, requiring tau inclusions in neurons and glia, with tau astrocytic plaques, and extensive thread-like pathology in both grey matter and white matter1.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1] Dickson, D. W. et al. Office of rare diseases neuropathologic criteria for corticobasal degeneration. J. Neuropathol. Exp. Neurol. 61, 935–946 (2002). source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationAssociation of CBD with the H1 haplotype was first reported in a series of 18 cases and subsequently confirmed in a larger autopsy series of 57 cases.
“An association of CBD with the H1 haplotype was first reported in a series of 18 cases (16 corticobasal syndrome patients and two autopsy-confirmed CBD cases)15 and subsequently confirmed in a larger autopsy series of 57 cases16.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [15] Di Maria, E. et al. Corticobasal degeneration shares a common genetic background with progressive supranuclear palsy. Ann. Neurol. 47, 374–377 (2000). source
- cites [16] Houlden, H. et al. Corticobasal degeneration and progressive supranuclear palsy share a common tau haplotype. Neurology 56, 1702–1706 (2001). source
Classified as probably not a substantial claim.
PremisecitationGenetic association studies of PSP have repeatedly shown increased risk for individuals carrying the H1 MAPT haplotype at chromosome 17q21.
“yet genetic association studies of PSP have repeatedly shown an increased risk for individuals carrying the H1 MAPT haplotype at chromosome 17q21 (refs 11, 12, 13, 14).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [11] Baker, M. et al. Association of an extended haplotype in the tau gene with progressive supranuclear palsy. Hum. Mol. Genet. 8, 711–715 (1999). source
- cites [12] Ezquerra, M. et al. Identification of a novel polymorphism in the promoter region of the tau gene highly associated to progressive supranuclear palsy in humans. Neurosci. Lett. 275, 183–186 (1999). source
- cites [13] Higgins, J. J. et al. An extended 5'-tau susceptibility haplotype in progressive supranuclear palsy. Neurology 55, 1364–1367 (2000). source
May combine two claims.
Interpretationown dataThe results indicate an overlap in genetic risk factors for PSP and CBD, but additional genetic variation differs between the two disorders.
“The results of the current study and those of the PSP GWAS indicate an overlap in genetic risk factors for PSP and CBD, but it appears that there is additional genetic variation that differs between the two disorders.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAll qPCR reactions were technically replicated.
“All qPCR reactions were technically replicated.”
Quote in the paperNot a substantial claim
The authors state this as an assumption.
Genotype frequencies are in Hardy–Weinberg equilibrium in CBD cases and control individuals separately, and association testing is performed using logistic regression under an additive model.
“The power assessment assumes that genotype frequencies are in Hardy–Weinberg equilibrium in CBD cases and control individuals separately and that association testing is performed using logistic regression under an additive model.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
SNPs within the H1 haplotype of the MAPT locus are associated with increased risk for CBD, PSP, and FTD.
“Recent genome-wide association studies (GWAS) have shown that single nucleotide polymorphisms (SNPs) within the H1 haplotype of the MAPT locus are associated with increased risk for CBD, PSP, and FTD [20, 24, 32].”
From Shared genetic risk between corticobasal degeneration, progressive supranuclear palsy, and frontotemporal dementia (2017) · cites this paper as [24]
The Results (Discovery GWAS and replication; page unavailable) report an association between the MAPT H1c-tagging SNP rs242557 and CBD. The Discussion (page unavailable) says this SNP was also associated with PSP. Our copy mentions FTD as a possible clinical presentation associated with other underlying disorders, but does not report an H1 MAPT risk association for FTD. (LLM, conf=0.90)
Experimental — accuracy not yet measuredGWAS of pathologically confirmed CBD cases and clinically and pathologically defined PSP cases have independently identified SNPs within MOBP as increasing disease risk.
“Additionally, GWAS of pathologically confirmed CBD cases and from clinically and pathologically defined PSP cases have independently identified SNPs within MOBP as increasing disease risk [24] indicating that shared genetic risk may explain susceptibility to tau aggregates.”
From Shared genetic risk between corticobasal degeneration, progressive supranuclear palsy, and frontotemporal dementia (2017) · cites this paper as [24]
The Results (page unavailable) identify a MOBP SNP associated with increased CBD risk in autopsy-proven cases, and the Discussion (page unavailable) reports MOBP risk estimates for both CBD and an earlier PSP GWAS. Our copy does not specify whether that PSP GWAS included both clinically and pathologically defined cases, so it does not establish that qualifier. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Normal-control count differs for expression study
MinorThe results describe 20 normal cases for the lnc-KIF13B-1 expression study, but the methods report 19 controls.
“RNA from superior frontal cortex of 22 CBD and 20 normal cases”
“CBD patients (n=22) and normal controls (n=19)”
Replication control count differs
MinorThe abstract reports 439 replication controls, while the study description reports 457.
“67 CBD cases and 439 controls in a replication stage”
“n=67 replication stage) compared with controls (n=3,311 discovery stage, n=457 replication stage)”
SOS1 locus is assigned to two chromosome arms
MinorThe discovery results place SOS1 at 2q22, whereas the abstract and other sections place the locus at 2p22.
“an intronic SNP in SOS1 on chromosome 2q22”
“2p22 at SOS1 (rs963731; P=1.76 × 10−7)”
Cites
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089 · see citing works
An integrated map of genetic variation from 1,092 human genomes
The 1000 Genomes Project Consortium (2012) · Nature · doi:10.1038/nature11632 · Cited by 7,711 · cited 1× · see citing works
“CBD cases and controls were imputed to samples from the 1000 Genomes Project (May 2011, European reference population) 20 .”
Mapping and analysis of chromatin state dynamics in nine human cell types
Ernst, J., Kheradpour, P., Mikkelsen, T. S., Shoresh, N., Ward, L. D., Epstein, C. B., Zhang, X., Wang, L., Issner, R., Coyne, M., et al. (2011) · Nature · doi:10.1038/nature09906 · Cited by 2,898 · cited 1× · see citing works
“…a tool for chromatin profiling, which allows one to explore the impact of non-coding variants, such as those identified in GWASs, by using in silico analysis coupled with experiments to validate biochemical and functional activators and repressors 24,25 .”
Self-citationLocusZoom: regional visualization of genome-wide association scan results
Pruim, R. J., Welch, R. P., Sanna, S., Teslovich, T. M., Chines, P. S., Gliedt, T. P., Boehnke, M., Abecasis, G. R., & Willer, C. J. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq419 · Cited by 2,707 · see citing works
Ward, L. D., & Kellis, M. (2012) · Nucleic Acids Research · doi:10.1093/nar/gkr917 · Cited by 2,229 · cited 1× · see citing works
“…a tool for chromatin profiling, which allows one to explore the impact of non-coding variants, such as those identified in GWASs, by using in silico analysis coupled with experiments to validate biochemical and functional activators and repressors 24,25 .”
Criteria for the diagnosis of corticobasal degeneration
Armstrong, M. J., Litvan, I., Lang, A. E., Bak, T. H., Bhatia, K. P., Borroni, B., Boxer, A. L., Dickson, D. W., Grossman, M., Hallett, M., et al. (2013) · Neurology · doi:10.1212/wnl.0b013e31827f0fd1 · Cited by 1,904 · cited 1× · see citing works
“Furthermore, autopsy-confirmed CBD cases can often present with several different clinical syndromes 3 , which are frequently associated with other underlying neurodegenerative disorders such as progressive supranuclear palsy (PSP), Alzheimer’s disease (AD), and frontotemporal dementia (FTD) 4 .”
Self-citationBrowning, B. L., & Browning, S. R. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.01.005 · Cited by 1,640 · see citing works
Genotype Imputation with Thousands of Genomes
Howie, B., Marchini, J., & Stephens, M. (2011) · G3 Genes|Genomes|Genetics · doi:10.1534/g3.111.001198 · Cited by 966 · see citing works
Association of an Extended Haplotype in the Tau Gene with Progressive Supranuclear Palsy
Baker, M., Litvan, I., Houlden, H., Adamson, J., Dickson, D., Perez-Tur, J., Hardy, J., Lynch, T., Bigio, E., & Hutton, M. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.4.711 · Cited by 781 · cited 1× · see citing works
“There are few reported families affected with CBD or PSP 8–10 , yet genetic association studies of PSP have repeatedly shown an increased risk for individuals carrying the H1 MAPT haplotype at chromosome 17q21 11–14 .”
Self-citationOffice of Rare Diseases Neuropathologic Criteria for Corticobasal Degeneration
Dickson, D. W., Bergeron, C., Chin, S. S., Duyckaerts, C., Horoupian, D., Ikeda, K., Jellinger, K., Lantos, P. L., Lippa, C. F., Mirra, S. S., et al. (2002) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/61.11.935 · Cited by 724 · cited 2× · see citing works
“Similar to progressive supranuclear palsy (PSP), Alzheimer’s disease (AD), and chronic traumatic encephalopathy (CTE), CBD is a tauopathy, having abnormal aggregates of microtubule-associated protein tau in the brain 1 .”
Self-citationCorticodentatonigral Degeneration With Neuronal Achromasia
Rebeiz, J. J., Kolodny, E. H., & Richardson, E. P. (1968) · Archives of Neurology · doi:10.1001/archneur.1968.00470310034003 · Cited by 627 · cited 1× · see citing works
“First described in 1968 by Rebeiz and colleagues, three CBD cases were identified to have a distinct movement disorder and neuropathologic profile 2 .”
Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy
PSP Genetics Study Group, Höglinger, G. U., Melhem, N. M., Dickson, D. W., Sleiman, P. M. A., Wang, L.-S., Klei, L., Rademakers, R., de Silva, R., Litvan, I., et al. (2011) · Nature Genetics · doi:10.1038/ng.859 · Cited by 603 · cited 7× · see citing works
“Testing for association using conditional logistic regression analysis with the top PSP GWAS SNPs identified rs1768208 (OR = 1.65, P = 3.86 × 10 −5 ), an intronic SNP in MOBP (myelin-associated oligodendrocytic basic protein), and rs242557 (OR = 1.48, P = 1.20 × 10 −3 ) at the MAPT locus to be associated with CBD.”
InfluentialSelf-citationPhosphoprotein Phosphatase Activities in Alzheimer Disease Brain
Gong, C., Singh, T. J., Grundke‐Iqbal, I., & Iqbal, K. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb03603.x · Cited by 527 · see citing works
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Pathologic heterogeneity in clinically diagnosed corticobasal degeneration
Boeve, B. F., Maraganore, D. M., Parisi, J. E., Ahlskog, J. E., Graff-Radford, N., Caselli, R. J., Dickson, D. W., Kokmen, E., & Petersen, R. C. (1999) · Neurology · doi:10.1212/wnl.53.4.795 · Cited by 417 · see citing works
Self-citationCorticobasal degeneration and progressive supranuclear palsy share a common tau haplotype
Houlden, H., Baker, M., Morris, H. R., MacDonald, N., Pickering–Brown, S., Adamson, J., Lees, A. J., Rossor, M. N., Quinn, N. P., Kertesz, A., et al. (2001) · Neurology · doi:10.1212/wnl.56.12.1702 · Cited by 409 · cited 1× · see citing works
“An association of CBD with the H1 haplotype was first reported in a series of 18 cases (16 corticobasal syndrome patients and 2 autopsy-confirmed CBD cases) 15 and subsequently confirmed in a larger autopsy series of 57 16 .”
Self-citationHaplotype Estimation Using Sequencing Reads
Delaneau, O., Howie, B., Cox, A. J., Zagury, J., & Marchini, J. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2013.09.002 · Cited by 396 · see citing works
Does corticobasal degeneration exist? A clinicopathological re-evaluation
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Corticobasal degeneration: a pathologically distinct 4R tauopathy
Kouri, N., Whitwell, J. L., Josephs, K. A., Rademakers, R., & Dickson, D. W. (2011) · Nature Reviews Neurology · doi:10.1038/nrneurol.2011.43 · Cited by 246 · cited 1× · see citing works
“This phenotypic variability results in less than 50% of patients with CBS having CBD at autopsy 5–7 .”
Self-citationA Novel Mitogen-activated Protein Kinase Phosphatase. STRUCTURE, EXPRESSION, AND REGULATION
Misra-Press, A., Rim, C. S., Yao, H. W., Roberson, M. S., & Stork, P. A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.24.14587 · Cited by 228 · cited 1× · see citing works
“…variants is in the gene STX6 , is a SNARE-class protein that regulates vesicle membrane fusion, which raises the possibility that dysfunction of vesicular trafficking may be a common disease mechanism between CBD and PSP. DUSP4 acts through tyrosine and threonine-directed dephosphorylation 31 .”
Brain Expression Genome-Wide Association Study (eGWAS) Identifies Human Disease-Associated Variants
Zou, F., Chai, H. S., Younkin, C. S., Allen, M., Crook, J. E., Pankratz, V. S., Carrasquillo, M. M., Rowley, C. N., Nair, A., Middha, S., et al. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002707 · Cited by 216 · cited 3× · see citing works
“The sample set was analyzed as a single cohort for maximum statistical power to detect associations, while including a covariate for AD diagnosis 23 .”
InfluentialSelf-citationRademakers, R., Melquist, S., Cruts, M., Theuns, J., Del-Favero, J., Poorkaj, P., Baker, M., Sleegers, K., Crook, R., De Pooter, T., et al. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi361 · Cited by 164 · cited 1× · see citing works
“In addition, CBD was also associated with rs242557 ( P = 7.91 × 10 −6 ), a SNP tagging the H1c subhaplotype at 17q21, shown to be associated with PSP and located in a regulatory region influencing MAPT expression 26 .”
InfluentialSelf-citationJosephs, K. A., & Dickson, D. W. (2003) · Movement Disorders · doi:10.1002/mds.10488 · Cited by 163 · see citing works
Self-citationTransport of PIP3 by GAKIN, a kinesin-3 family protein, regulates neuronal cell polarity
Horiguchi, K., Hanada, T., Fukui, Y., & Chishti, A. H. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200604031 · Cited by 157 · see citing works
Signature Tau Neuropathology in Gray and White Matter of Corticobasal Degeneration
Forman, M. S., Zhukareva, V. A., Bergeron, C., Chin, S. S., Grossman, M., Clark, C. M., Lee, V. M. ‐., & Trojanowski, J. Q. (2002) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)61154-6 · Cited by 149 · cited 1× · see citing works
“Because tau phosphorylation plays a critical role in tauopathies, 32 it will be interesting if DUSP4 is responsible for the genetic association at 8p12.”
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“KIF13B is a plus end-directed microtubule motor protein highly expressed in the brain, and is involved in synaptic vesicle trafficking along microtubules, neurite extension, and caveolin-dependent endocytosis 28–30 .”
Kouri, N., Murray, M. E., Hassan, A., Rademakers, R., Uitti, R. J., Boeve, B. F., Graff‐Radford, N. R., Wszołek, Z. K., Litvan, I., Josephs, K. A., et al. (2011) · Brain · doi:10.1093/brain/awr234 · Cited by 133 · cited 1× · see citing works
“Furthermore, autopsy-confirmed CBD cases can often present with several different clinical syndromes 3 , which are frequently associated with other underlying neurodegenerative disorders such as progressive supranuclear palsy (PSP), Alzheimer’s disease (AD), and frontotemporal dementia (FTD) 4 .”
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“…the first non-MAPT genetic risk factor shared between CBD and PSP. Yamamoto et al. described MOBP as one of the most abundant oligodendrocyte-expressing proteins, similar to myelin basic protein, with the main difference being that MOBP is only expressed in myelin of the central nervous system 27 .”
Novel mutation in MAPT exon 13 (p.N410H) causes corticobasal degeneration
Kouri, N., Carlomagno, Y., Baker, M., Liesinger, A. M., Caselli, R. J., Wszołek, Z. K., Petrucelli, L., Boeve, B. F., Parisi, J. E., Josephs, K. A., et al. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1193-7 · Cited by 82 · cited 2× · see citing works
“There are few reported families affected with CBD or PSP 8–10 , yet genetic association studies of PSP have repeatedly shown an increased risk for individuals carrying the H1 MAPT haplotype at chromosome 17q21 11–14 .”
Self-citationKIF13B enhances the endocytosis of LRP1 by recruiting LRP1 to caveolae
Kanai, Y., Wang, D., & Hirokawa, N. (2014) · The Journal of Cell Biology · doi:10.1083/jcb.201309066 · Cited by 81 · cited 1× · see citing works
“KIF13B is a plus end-directed microtubule motor protein highly expressed in the brain, and is involved in synaptic vesicle trafficking along microtubules, neurite extension, and caveolin-dependent endocytosis 28–30 .”
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Three sib-pairs of autopsy-confirmed progressive supranuclear palsy
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“The disadvantage of applying stringent criteria is the possibility of false-negative associations, as evidenced from the power analysis, which show low power to detect genome-wide associations of variants with modest effect sizes (Supplementary Tables 8 and 9).”
Self-citationAn extended 5′- <i>tau</i> susceptibility haplotype in progressive supranuclear palsy
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Self-citationThe tau gene A0 allele and progressive supranuclear palsy
Hoenicka, J., Pérez, M., Pérez‐Tur, J., Barabash, A., de Godoy, M. F., Vidal, L., Astarloa, R., Ávila, J., Nygaard, T. G., & de Yébenes, J. G. (1999) · Neurology · doi:10.1212/wnl.53.6.1219 · Cited by 48 · cited 1× · see citing works
“There are few reported families affected with CBD or PSP 8–10 , yet genetic association studies of PSP have repeatedly shown an increased risk for individuals carrying the H1 MAPT haplotype at chromosome 17q21 11–14 .”
A familial form of parkinsonism, dementia, and motor neuron disease: A longitudinal study
Fujioka, S., Boeve, B. F., Parisi, J. E., Tacik, P. M., Aoki, N., Strongosky, A. J., Baker, M. C., Sánchez-Contreras, M., Ross, O. A., Rademakers, R., et al. (2014) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2014.07.014 · Cited by 6 · cited 2× · see citing works
“There are few reported families affected with CBD or PSP 8–10 , yet genetic association studies of PSP have repeatedly shown an increased risk for individuals carrying the H1 MAPT haplotype at chromosome 17q21 11–14 .”
Self-citationCann, S. A. H., Netten, J. P. V., & Netten, C. V. (2000) · Pure Amsterdam UMC · doi:10.1002/1531-8249(200003)47:3
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Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria
Höglinger, G. U., Respondek, G., Stamelou, M., Kurz, C., Josephs, K. A., Lang, A. E., Mollenhauer, B., Müller, U., Nilsson, C., Whitwell, J. L., et al. (2017) · Movement Disorders · doi:10.1002/mds.26987 · Cited by 2,374 · see citing works
Self-citationA practical guide to linking brain-wide gene expression and neuroimaging data
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Propagation of Tau aggregates and neurodegeneration
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Self-citationNovel tau filament fold in corticobasal degeneration
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Self-citationConverging pathways in neurodegeneration, from genetics to mechanisms
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MAPT mutations, tauopathy, and mechanisms of neurodegeneration
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Genetics of Parkinson's disease
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“progressive supranuclear palsy (106) and corticobasal degeneration (107).”
BackgroundTau and neuroinflammation: what impact for Alzheimer's disease and tauopathies?
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BackgroundA walk through tau therapeutic strategies
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Common genetic variation influencing human white matter microstructure
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“In these regions, white matter–associated variants colocalized with risk variants of many brain disorders and cognition, such as schizophrenia (53), Alzheimer’s disease (54), corticobasal degeneration (55), Parkinson’s disease (56), progressive supranuclear palsy (55), ASD (57), alcohol use disorder (58), depression (…”
Background(2018) · Handbook of Clinical Neurology · doi:10.1016/b978-0-12-802395-2.00025-0 · Cited by 225 · see citing works
Rösler, T. W., Marvian, A. T., Brendel, M., Nykänen, N.-P., Höllerhage, M., Schwarz, S. C., Hopfner, F., Koeglsperger, T., Respondek, G., Schweyer, K., et al. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2019.101644 · Cited by 219 · see citing works
Self-citationCellular and pathological heterogeneity of primary tauopathies
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Self-citationTauopathies as clinicopathological entities
Irwin, D. J. (2015) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2015.09.020 · Cited by 199 · see citing works
“PART appears to lack association with AD-associated risk polymorphism in apolipoprotein gene (ε4) while having a genetic risk associated withMAPT tau H1 haplotype, and can be associated with minimal or no cognitive impairment in older patients [7].”
InfluentialBroce, I., Karch, C. M. M., Wen, N., Fan, C. C., Wang, Y., Tan, C. H., Kouri, N., Ross, O. A., Höglinger, G. U., Müller, U., et al. (2018) · PLoS Medicine · doi:10.1371/journal.pmed.1002487 · Cited by 184 · see citing works
“We obtained CBD GWAS summary statistic data from 152 CBD cases and 3,311 controls at 533,898 SNPs (Table 1; for additional details, see [18]).”
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Retiring the term FTDP-17 as MAPT mutations are genetic forms of sporadic frontotemporal tauopathies
Forrest, S. L., Kril, J. J., Stevens, C. H., Kwok, J. B., Hallupp, M., Kim, W. S., Huang, Y. M., McGinley, C. V., Werka, H., Kiernan, M. C., et al. (2017) · Brain · doi:10.1093/brain/awx328 · Cited by 148 · see citing works
“…and genetic overlap between CBD and PSP (Katsuse et al., 2003; Lang, 2003; Tan et al., 2005; Jung et al., 2012) with genome wide association studies showing that common polymorphisms in MAPT, MOBP and VEGFA increase the risk for both CBD and PSP (Borroni et al., 2010; Kouri et al., 2014, 2015).”
BackgroundO’Brien, H., Hannon, E. J., Hill, M., Toste, C., Robertson, M. J., Morgan, J., McLaughlin, G. M., Lewis, C. M., Schalkwyk, L. C., Hall, L. S., et al. (2018) · Genome biology · doi:10.1186/s13059-018-1567-1 · Cited by 146 · see citing works
“Variants within this inversion (denoted “ H2 ” ), which appears to be under positive selection in Europeans [22], have recently been implicated in neuroticism [24 – 26], while markers on the non-inverted form (denoted “ H1 ” ) are associated with several neurodegenerative diseases [27 – 29].”
Conserved brain myelination networks are altered in Alzheimer’s and other neurodegenerative diseases
Allen, M., Wang, X., Burgess, J. D., Watzlawik, J., Serie, D. J., Younkin, C. S., Nguyen, T., Malphrus, K. G., Lincoln, S., Carrasquillo, M. M., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2017.09.012 · Cited by 143 · see citing works
“Indeed, variants in/near MOBP are implicated in risk of PSP [34] and CBD [40], another 4R-tauopathy.”
Self-citationEvolving concepts in progressive supranuclear palsy and other 4-repeat tauopathies
Stamelou, M., Respondek, G., Giagkou, N., Whitwell, J. L., Kovács, G. G., & Höglinger, G. U. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00541-5 · Cited by 143 · see citing works
Self-citationTsai, R. M., Miller, Z., KOESTLER, M. E., Rojas, J. C., Ljubenkov, P. A., Rosen, H. J., Rabinovici, G. D., Fagan, A. M., Cobigo, Y., Brown, J. A., et al. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2019.3812 · Cited by 134 · see citing works
“SEADL scoreh NA NA NA NA NA 40 (10-100) 20 (10-50) 60 (30-100) 60 (10-90) 50 (30-80) 45 (10-100)”
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Mitochondrial dysfunction in Parkinsonian mesenchymal stem cells impairs differentiation
Angelova, P. R., Barilani, M., Lovejoy, C. E. J., Dossena, M., Viganò, M., Seresini, A., Piga, D., Gandhi, S., Pezzoli, G., Abramov, A. Y., et al. (2017) · Redox Biology · doi:10.1016/j.redox.2017.10.016 · Cited by 119 · see citing works
Tau deposition patterns are associated with functional connectivity in primary tauopathies
Franzmeier, N., Brendel, M., Beyer, L., Slemann, L., Kovács, G. G., Arzberger, T., Kurz, C., Respondek, G., Ječmenica‐Lukić, M., Biel, D., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28896-3 · Cited by 112 · see citing works
Self-citationGenetics of neurodegenerative diseases: an overview
Pihlstrøm, L., Wiethoff, S., & Houlden, H. (2017) · Handbook of clinical neurology · doi:10.1016/b978-0-12-802395-2.00022-5 · Cited by 116 · see citing works
“APOE and a few other important susceptibility loci, including SNCA and MAPT in PD (Kruger et al., 1999; Martin et al., 2001; Maraganore et al., 2006), were discovered in candidate gene studies, yet the characterization of common risk variants on a larger scale has been achieved through GWAS.”
Tau biology, tauopathy, traumatic brain injury, and diagnostic challenges
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Progressive supranuclear palsy: Advances in diagnosis and management
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Self-citationInternational FTD-Genomics Consortium (IFGC), Yokoyama, J. S., Karch, C. M., Fan, C. C., Bonham, L. W., Kouri, N., Ross, O. A., Rademakers, R., Kim, J., Wang, Y., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1693-y · Cited by 99 · see citing works
“Building on these findings, we additionally found that our CBD, PSP, and FTD shared risk genes were enriched for several neurodevelopmental processes including neuron migration, tubulin complex, and neuron projection morphogenesis.”
BackgroundInfluentialSelf-citationGenetics of common cerebral small vessel disease
Bordes, C., Sargurupremraj, M., Mishra, A., & Debette, S. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-021-00592-8 · Cited by 101 · see citing works
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Progressive Supranuclear Palsy: an Update
Armstrong, M. J. (2018) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-018-0819-5 · Cited by 92 · see citing works
Tau at the interface between neurodegeneration and neuroinflammation
Didonna, A. (2020) · Genes & Immunity · doi:10.1038/s41435-020-00113-5 · Cited by 82 · see citing works
Karch, C. M., Wen, N., Fan, C. C., Yokoyama, J. S., Kouri, N., Ross, O. A., Höglinger, G., Müller, U., Ferrari, R., Hardy, J., et al. (2018) · JAMA Neurology · doi:10.1001/jamaneurol.2018.0372 · Cited by 89 · see citing works
“34 While SNPs that tag the H1 haplotype of MAPT have been associated with increased risk for FTD, PSP, CBD, AD and PD 10,11,13,16-18 , this is the first report of an association between MAPT H1 and ALS risk.”
Self-citationEye-brain connections revealed by multimodal retinal and brain imaging genetics
Zhao, B., Li, Y., Fan, Z., Wu, Z., Shu, J., Yang, X., Yang, Y., Wang, X., Li, B., Wang, X., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-50309-w · Cited by 90 · see citing works
Atypical parkinsonian syndromes: a general neurologist's perspective
Deutschländer, A., Ross, O. A., Dickson, D. W., & Wszołek, Z. K. (2017) · European Journal of Neurology · doi:10.1111/ene.13412 · Cited by 81 · see citing works
“The largest GWAS performed in CBD found associations at MAPT, SOS1 and at a chromosome 8p12 locus (including the genes lnc-KIF13B-1, DUSP4 and KIF13B) [66].”
BackgroundSelf-citationTau and MAPT genetics in tauopathies and synucleinopathies
Léveillé, E., Ross, O. A., & Gan‐Or, Z. (2021) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2021.09.008 · Cited by 83 · see citing works
Self-citationAllen, M., Burgess, J. D., Ballard, T., Serie, D., Wang, X., Younkin, C. S., Sun, Z., Kouri, N., Baheti, S., Wang, C., et al. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1576-7 · Cited by 78 · see citing works
“The extent of LD in the MAPT region poses great difficulty in discerning the gene(s) and functional variants that impose risk for PSP and other neurodegenerative diseases that associate with SNPs in this region, such as Alzheimer’s (AD) [1, 24, 31] and Parkinson’s disease (PD) [11, 40].”
Self-citationGenetics of Progressive Supranuclear Palsy
Im, S. Y., Kim, Y. E., & Kim, Y. J. (2015) · Journal of Movement Disorders · doi:10.14802/jmd.15033 · Cited by 76 · see citing works
Primary Tau Pathology, Not Copathology, Correlates With Clinical Symptoms in PSP and CBD
Robinson, J. L., Yan, N., Caswell, C., Xie, S. X., Suh, E. R., Deerlin, V. M. V., Gibbons, G. S., Irwin, D. J., Grossman, M., Lee, E. B., et al. (2019) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlz141 · Cited by 75 · see citing works
Self-citationKoga, S., Kouri, N., Walton, R. L., Ebbert, M., Josephs, K. A., Litvan, I., Graff‐Radford, N. R., Ahlskog, J. E., Uitti, R. J., van Gerpen, J. A., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1878-z · Cited by 75 · see citing works
“In addition, both diseases share genetic risk factors, including H1 haplotype of the MAPT gene [4, 9, 19, 35, 64].”
BackgroundSelf-citationJiang, S., Wen, N., Li, Z., Dube, U., Del Aguila, J., Budde, J., Martinez, R., Hsu, S., Fernandez, M. V., Cairns, N. J., et al. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0319-z · Cited by 73 · see citing works
Cellular and regional vulnerability in frontotemporal tauopathies
Forrest, S. L., Kril, J. J., & Halliday, G. M. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02035-7 · Cited by 72 · see citing works
Recent Advances in the Genetics of Frontotemporal Dementia
Sirkis, D. W., Geier, E. G., Bonham, L. W., Karch, C. M. M., & Yokoyama, J. S. (2019) · Current Genetic Medicine Reports · doi:10.1007/s40142-019-0160-6 · Cited by 68 · see citing works
Lebouvier, T., Pasquier, F., & Buée, L. (2017) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000502 · Cited by 68 · see citing works
The ordered assembly of tau is the gain‐of‐toxic function that causes human tauopathies
Goedert, M. (2016) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2016.09.001 · Cited by 62 · see citing works
Cali, C. P., Patiño, M., Tai, Y., Ho, W. Y., Mclean, C., Morris, C., Seeley, W., Miller, B., Gaig, C., Vonsattel, J., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02045-5 · Cited by 55 · see citing works
Self-citationAllen, M., Wang, X., Serie, D., Strickland, S. L., Burgess, J. D., Koga, S., Younkin, C. S., Nguyen, T., Malphrus, K. G., Lincoln, S., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1900-5 · Cited by 58 · see citing works
Self-citationBowles, K. R., Pugh, D. A., Liu, Y., Patel, T., Renton, A. E., Bandrés‐Ciga, S., Gan‐Or, Z., Heutink, P., Siitonen, A., Bertelsen, S. E., et al. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00551-x · Cited by 57 · see citing works
“Furthermore, in contrast to PSP and CBD, PD has not been associated with the H1c subhaplotype [18, 19] and is not generally associated with the accumulation of tau.”
BackgroundInfluentialMechanisms of Neurodegeneration in Various Forms of Parkinsonism—Similarities and Differences
Koziorowski, D., Figura, M., Milanowski, Ł., Szlufik, S., Alster, P., Madetko‐Alster, N., & Friedman, A. (2021) · Cells · doi:10.3390/cells10030656 · Cited by 59 · see citing works
“A positive correlation with MAPT was also observed in another tauopathy—CBD [92].”
BackgroundDivergent Patterns of TDP-43 and Tau Pathologies in Primary Progressive Aphasia
Giannini, L. A. A., Xie, S. X., McMillan, C., Liang, M., Williams, A., Jester, C., Rascovsky, K., Wolk, D., Ash, S., Lee, E. B., et al. (2019) · Annals of Neurology · doi:10.1002/ana.25465 · Cited by 46 · see citing works
Self-citationGene and Network Analysis of Common Variants Reveals Novel Associations in Multiple Complex Diseases
Nakka, P., Raphael, B. J., & Ramachandran, S. (2016) · Genetics · doi:10.1534/genetics.116.188391 · Cited by 55 · see citing works
“…of moderate to small effect (Hirschhorn and Daly 2005; McCarthy et al. 2008; Daly 2010; Jiang et al. 2012; Evangelou and Ioannidis 2013; Nalls et al. 2014; Skibola et al. 2014; Woo et al. 2014; Buch et al. 2015; Kouri et al. 2015; Litchfield et al. 2015; Renton et al. 2015; Hallberg et al. 2016).”
BackgroundBeevers, J. E., Lai, M. C., Collins, E., Booth, H., Zambon, F., Parkkinen, L., Vowles, J., Cowley, S. A., Wade‐Martins, R., & Caffrey, T. M. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.06.005 · Cited by 53 · see citing works
“Tauopathies show differing aggregation compositions of tau protein, with principally 4R tau aggregating in PSP, CBD, and frontotemporal dementia with Parkinsonism associated with chromosome 17 (FTDP-17) (Arai et al., 2001; Buee Scherrer et al., 1996); 3R tau proteins aggregating in Pick’s disease (Delacourte et al., 1…”
BackgroundInfluentialJellinger, K. A. (2019) · Journal of Neural Transmission · doi:10.1007/s00702-019-02028-6 · Cited by 55 · see citing works
Bettencourt, C., Foti, S. C., Miki, Y., Botía, J. A., Chatterjee, A., Warner, T. T., Révész, T., Lashley, T., Balázs, R., Viré, E. A., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02074-0 · Cited by 53 · see citing works
Mizuno, A., & Okada, Y. (2019) · European Journal of Human Genetics · doi:10.1038/s41431-019-0468-4 · Cited by 52 · see citing works
Farrell, K. W., Humphrey, J., Chang, T. S., Zhao, Y., Leung, Y. Y., Kuksa, P. P., Patil, V., Lee, W., Kuzma, A. B., Valladares, O., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-52025-x · Cited by 51 · see citing works
Self-citationSaranza, G., Whitwell, J. L., Kovács, G. G., & Lang, A. E. (2019) · International review of neurobiology · doi:10.1016/bs.irn.2019.10.014 · Cited by 48 · see citing works
A Review of Biomarkers for Neurodegenerative Disease: Will They Swing Us Across the Valley?
Beach, T. G. (2017) · Neurology and Therapy · doi:10.1007/s40120-017-0072-x · Cited by 47 · see citing works
“In large genome-wide studies, the inaccuracy of the clinical diagnostic gold standard has been overcome by huge sample size, but it has been recognized that genomic studies utilizing subjects with a neuropathological diagnosis, because of the more precise molecular phenotyping, may be done with much smaller subject nu…”
BackgroundMAPT haplotype H1G is associated with increased risk of dementia with Lewy bodies
Labbé, C., Heckman, M. G., Lorenzo‐Betancor, O., Soto‐Ortolaza, A. I., Walton, R. L., Murray, M. E., Allen, M., Uitti, R. J., Wszołek, Z. K., Smith, G. E., et al. (2016) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2016.05.002 · Cited by 45 · see citing works
“The H2 haplotype has been associated with a decreased risk of PD [13], progressive supranuclear palsy (PSP) [14] and corticobasal degeneration [15] through genome-wide association studies.”
BackgroundSelf-citationGenome-wide association study identifies MAPT locus influencing human plasma tau levels
Chen, J., Yu, J., Wojta, K. J., Wang, H.-F., Zetterberg, H., Blennow, K., Yokoyama, J. S., Weiner, M. W., Kramer, J. H., Rosen, H. J., et al. (2017) · Neurology · doi:10.1212/wnl.0000000000003615 · Cited by 46 · see citing works
“Moreover, the common subhaplotype H1c (tagged by rs242557) on the background of the H1 haplotype has been consistently found to be associated with both PSP and CBD.(12,15,16,20) Previously published GWAS data with neuropathologically diagnosed cases showed that rs242557, tagging the MAPT H1c haplotype, was one of the…”
ResultInfluentialGenome‐wide survey of copy number variants finds MAPT duplications in progressive supranuclear palsy
Chen, Z., Chen, J., Shatunov, A., Jones, A. R., Kravitz, S. N., Huang, A., Lawrence, L., Lowe, J. K., Lewis, C. M., Payan, C., et al. (2019) · Movement Disorders · doi:10.1002/mds.27702 · Cited by 43 · see citing works
“30 × 10) in the replication stage.(28) Furthermore, a risk locus in MOBP has been confirmed to be associated at genome-wide significance with amyotrophic lateral sclerosis (ALS).”
BackgroundWang, X., Campbell, M. R., Lacher, S. E., Cho, H.-Y., Wan, M., Crowl, C. L., Chorley, B. N., Bond, G. L., Kleeberger, S. R., Slattery, M., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.03.068 · Cited by 49 · see citing works
“…strongest GWAS signal (p = 1.5×10−116 (Hoglinger et al., 2011)) for progressive supranuclear palsy, and very strong signal for Parkinson’s disease (p = 7.0×10−12 (Spencer et al., 2011), corticobasal degeneration (p = 1.3×10−8 (Kouri et al., 2015)) and Alzheimer’s (p=5.2×10−5 (Allen et al., 2014)).”
InfluentialHe, L., Loika, Y., Park, Y., Bennett, D. A., Kellis, M., Kulminski, A. M., & Initiative, A. D. N. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01263-4 · Cited by 40 · see citing works
“3835 (58) 3248 (704) 2218 (1622) 531 (2208)”
Unraveling the complex role of MAPT-containing H1 and H2 haplotypes in neurodegenerative diseases
Pedicone, C., Weitzman, S. A., Renton, A. E., & Goate, A. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00731-x · Cited by 42 · see citing works
“…odds ratios (ORs) for PSP (OR = 5.46 for H1 relative to H2; OR = 1.91 for H1c relative to other H1 sub-haplotypes) [36, 37] and CBD (OR = 3.7) [32] risk, with lower odds ratios for AD (OR = 1.06) [74], PD (OR = 1.30) [35, 75], and behavioral variant FTD (bvFTD) (OR = 1.2) [76] risk (Table 2).”
BackgroundInfluentialEmerging Diagnostic and Therapeutic Strategies for Tauopathies
Coughlin, D. G., & Irwin, D. J. (2017) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-017-0779-1 · Cited by 39 · see citing works
Corticobasal degeneration: key emerging issues
Ali, F., & Josephs, K. A. (2017) · Journal of Neurology · doi:10.1007/s00415-017-8644-3 · Cited by 37 · see citing works
“association study of autopsy proven CBD cases found an association with single nucleotide polymorphisms (SNPs) in MAPT H1 haplotype (rs242557, rs393152, rs8070723) and MOBP (myelin associated oligodendrocyte basic protein)- a Rab GTPase involved in myelin sheath stabilization (SNP: rs1768208) [17].”
BackgroundSelf-citationFrontrunner in Translation: Progressive Supranuclear Palsy
Shoeibi, A., Olfati, N., & Litvan, I. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.01125 · Cited by 39 · see citing works
“Sometimes these patients are clinically indistinguishable from patients with CBD-CBS, but the early presence of supranuclear vertical gaze palsy/slow vertical saccade or postural instability may favor the PSP-CBS diagnosis (45–48).”
BackgroundInfluentialSelf-citationMAPT haplotype–stratified GWAS reveals differential association for AD risk variants
Strickland, S. L., Reddy, J. S., Allen, M., N’Songo, A., Burgess, J. D., Corda, M. M., Ballard, T., Wang, X., Carrasquillo, M. M., Biernacka, J. M., et al. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12099 · Cited by 35 · see citing works
“In addition, MAPT H1 haplotype shows considerable variation 10,11 and leads to H1-subhaplotypes, where H1c, has been implicated in the risk of PSP, CBD, AD, and PD. 12,13 MAPT H2 haplotype has been associated with reduced risk for several neurodegenerative disorders.”
Self-citationGenome-wide association study and functional validation implicates JADE1 in tauopathy
Farrell, K. W., Kim, S., Han, N., Iida, M. A., Gonzalez, E. M., Otero‐García, M., Walker, J. M., Richardson, T. E., Renton, A. E., Andrews, S. J., et al. (2021) · Acta Neuropathologica · doi:10.1007/s00401-021-02379-z · Cited by 36 · see citing works
Self-citationEpidemiology of atypical parkinsonian syndromes
Lo, R. Y. (2021) · Tzu Chi Medical Journal · doi:10.4103/tcmj.tcmj_218_20 · Cited by 34 · see citing works
“A GWAS study based on 152 autopsy-proven CBD cases and 3311 controls identified risk variants shared with PSP, including MAPT H1c (17q21; rs242557) and MOBP (3p22; rs1768208), suggesting that certain genetic susceptibility does exist in CBD [142].”
MethodMaphis, N. M., Jiang, S., Binder, J., Wright, C., Gopalan, B., Lamb, B. T., & Bhaskar, K. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00069 · Cited by 34 · see citing works
“The dilutions of primary antibodies utilized were as follows: GAPDH at 1:20,000; Tau5 at 1:10,000; phospho- and total-MECP2 at 1:1000.”
BackgroundTau Seeding Mouse Models with Patient Brain-Derived Aggregates
Robert, A., Schöll, M., & Vogels, T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22116132 · Cited by 35 · see citing works
Clinicopathological overlap of neurodegenerative diseases: A comprehensive review
Das, S. K., Zhang, Z., & Ang, L. C. (2020) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2020.04.088 · Cited by 33 · see citing works
Höglinger, G. U. (2017) · Movement Disorders Clinical Practice · doi:10.1002/mdc3.12582 · Cited by 32 · see citing works
Self-citationGenetics of Parkinson's Disease: From Causes to TreatmentPreprint
Westenberger, A., Brüggemann, N., & Klein, C. (2024) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041774 · Cited by 34 · see citing works
Progressive Supranuclear Palsy and Corticobasal Degeneration
Coughlin, D. G., Dickson, D. W., Josephs, K. A., & Litvan, I. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-51140-1_11 · Cited by 32 · see citing works
Self-citationConserved gene signatures shared among MAPT mutations reveal defects in calcium signaling
Minaya, M., Mahali, S. K., Iyer, A. K., Eteleeb, A. M., Martinez, R. J., Huang, G., Budde, J., Temple, S., Nana, A. L., Seeley, W. W., et al. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1051494 · Cited by 26 · see citing works
“Common genetic variation in the MAPT gene also contributes to sporadic forms of FTLD-Tau, including progressive supranuclear palsy (PSP) and corticobasal degeneration (Ferrari et al., 2014; Kouri et al., 2015; Steele et al., 2018).”
BackgroundSelf-citationGenetics Underlying Atypical Parkinsonism and Related Neurodegenerative Disorders
Scholz, S. W., & Brás, J. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms161024629 · Cited by 29 · see citing works
“Data from a recent small-sized GWAS support the notion of a genetic contribution to the pathogenesis of the more common sporadic form of CBD [208].”
BackgroundGene regulatory effects of disease-associated variation in the NRF2 network
Lacher, S. E., & Slattery, M. G. (2016) · Current Opinion in Toxicology · doi:10.1016/j.cotox.2016.09.001 · Cited by 27 · see citing works
MAPT haplotype diversity in multiple system atrophy
Labbé, C., Heckman, M. G., Lorenzo‐Betancor, O., et al. (2016) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2016.06.010 · Cited by 28 · see citing works
“The common H1 risk haplotype has been associated to increased risk of several neurodegenerative diseases such as PD [9], progressive supranuclear palsy (PSP) [10], and corticobasal degeneration (CBD) [11] in genome-wide association studies (GWAS).”
BackgroundSelf-citationAssessment of APOE in atypical parkinsonism syndromes
Sabir, M. S., Blauwendraat, C., Ahmed, S., Serrano, G. E., Beach, T. G., Perkins, M., Rice, A. C., Masliah, E., Morris, C. M., Pihlstrom, L., et al. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.02.016 · Cited by 28 · see citing works
Corticobasal syndrome: a practical guide
Wilson, D., Le Heron, C., & Anderson, T. (2021) · Practical Neurology · doi:10.1136/practneurol-2020-002835 · Cited by 25 · see citing works
Unravelling Genetic Factors Underlying Corticobasal Syndrome: A Systematic Review
Arienti, F., Lazzeri, G., Vizziello, M., Monfrini, E., Bresolin, N., Saetti, M. C., Picillo, M., Franco, G., & Fonzo, A. D. (2021) · Cells · doi:10.3390/cells10010171 · Cited by 27 · see citing works
“[90] performed a genomewide association study (GWAS) of 152 pathologically confirmed CBD cases and identified SNPs at 3p22 MOBP, showing another genetic risk factor shared by CBD and PSP.”
BackgroundProgressive Supranuclear Palsy Syndrome: An Overview
Ichikawa-Escamilla, E., Velasco-Martínez, R. A., & Adalid-Peralta, L. V. (2024) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2024.04.008 · Cited by 26 · see citing works
“The H1 haplotype increases the risk of developing the disease (Baker et al., 1999; Kouri et al., 2015), to the point that it has been considered the strongest risk factor (H ¨ oglinger et al., 2011).”
BackgroundValentino, R. R., Scotton, W. J., Roemer, S. F., Lashley, T., Heckman, M. G., Shoai, M., Martínez-Carrasco, A., Tamvaka, N., Walton, R. L., Baker, M., et al. (2024) · The Lancet Neurology · doi:10.1016/s1474-4422(24)00083-8 · Cited by 25 · see citing works
Self-citationNeuropathologic basis of frontotemporal dementia in progressive supranuclear palsy
Sakae, N., Josephs, K. A., Litvan, I., Murray, M. E., Duara, R., Uitti, R. J., Wszołek, Z. K., Graff‐Radford, N. R., & Dickson, D. W. (2019) · Movement Disorders · doi:10.1002/mds.27816 · Cited by 23 · see citing works
“Regarding white matter pathology in PSP and specifically in PSP-FTD, genome-wide association studies of PSP and CBD identified a variant near MOBP, a myelin oligodendrocyte protein.(29,30) It is of note that neuroimaging studies have suggested that white-matter abnormalities may correlate with apathy and impulsivity i…”
BackgroundSelf-citationThe Role of PERK in Understanding Development of Neurodegenerative Diseases
Smedley, G. D., Walker, K. E., & Yuan, S. H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22158146 · Cited by 24 · see citing works
“Several genome-wide association study (GWAS) were completed for PSP [57,91,92].”
BackgroundSiokas, V., Aloizou, A., Liampas, I., Bakirtzis, C., Tsouris, Z., Sgantzos, M. N., Liakos, P., Bogdanos, D. P., Hadjigeorgiou, G. M., & Dardiotis, E. (2021) · Acta Neurologica Scandinavica · doi:10.1111/ane.13538 · Cited by 24 · see citing works
Valentino, R. R., Koga, S., Walton, R. L., Soto‐Beasley, A. I., Kouri, N., Deture, M. A., Murray, M. E., Johnson, P. W., Petersen, R. C., Boeve, B. F., et al. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-01097-z · Cited by 23 · see citing works
Self-citationCognitive dysfunction in corticobasal degeneration
de Oliveira, L. M., Barcellos, I., Teive, H. A. G., & Munhoz, R. P. (2017) · Arquivos de Neuro-Psiquiatria · doi:10.1590/0004-282x20170077 · Cited by 22 · see citing works
Immunoreactivity of myelin‐associated oligodendrocytic basic protein in Lewy bodies
Kon, T., Tanji, K., Mori, F., Kimura, A., Kakita, A., & Wakabayashi, K. (2019) · Neuropathology · doi:10.1111/neup.12564 · Cited by 21 · see citing works
Neuronal MAPT expression is mediated by long-range interactions with cis-regulatory elements
Rogers, B. B., Anderson, A. G., Lauzon, S. N., Davis, M. N., Hauser, R. M., Roberts, S. C., Rodríguez-Nunez, I., Trausch‐Lowther, K., Barinaga, E. A., Hall, P. I., et al. (2024) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2023.12.015 · Cited by 21 · see citing works
A microglia clonal inflammatory disorder in Alzheimer’s disease
Vicario, R., Fragkogianni, S., Weber, L., Lazarov, T., Hu, Y., Hayashi, S. Y., Craddock, B., Socci, N. D., Alberdi, A., Baako, A., et al. (2025) · eLife · doi:10.7554/elife.96519.3 · Cited by 21 · see citing works
“…with neurodegenerativediseases (n=140) ( Bras et al., 2012 ; Renton et al., 2014 ; Karch et al., 2014 ; Karch and Goate, 2015 ; Turner et al., 2013 ; Ferrari et al., 2015 ; Kouri et al., 2015 ; Scholz and Bras, 2015 ; Nalls et al., 2014 ; Supplementary file 2 , see Materials and methods).”
InfluentialManzoni, C., Kia, D. A., Ferrari, R., Leonenko, G., Costa, B., Saba, V., Jabbari, E., Tan, M. M. X., Albani, D., Álvarez, V., et al. (2024) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2024.05.017 · Cited by 21 · see citing works
Self-citationDifferent MAPT haplotypes influence expression of total MAPT in postmortem brain tissue
Tauber, C. V. I., Schwarz, S. C., Rösler, T. W., Arzberger, T., Gentleman, S., Windl, O., Krumbiegel, M., Reis, A., Ruf, V., Herms, J. W., et al. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01534-9 · Cited by 21 · see citing works
Self-citationChinese nutraceuticals and physical activity; their role in neurodegenerative tauopathies
Alausa, A. O., Ogundepo, S., Olaleke, B., Adeyemi, R. O., Olatinwo, M., & Ismail, A. (2021) · Chinese Medicine · doi:10.1186/s13020-020-00418-7 · Cited by 20 · see citing works
“31 chromosome is the hallmark of CBD emergence, postmortem examination of CBD patients observed a connection between single nucleotide polymorphisms (SNPs) in MAPT H1 haplotype and the hydrolyzing enzyme Rab GTpase, acting on myelin associated oligodendrocyte basic proteins (MOBP), essential in the effective functioni…”
BackgroundGenetic Architecture of Primary Tauopathies
Gallo, D., Ruiz, A., & Sánchez‐Juan, P. (2022) · Neuroscience · doi:10.1016/j.neuroscience.2022.05.022 · Cited by 22 · see citing works
Respondek, G., Levin, J., & Höglinger, G. (2018) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000581 · Cited by 15 · see citing works
Self-citationGenetic susceptibility variants in parkinsonism
Soto‐Ortolaza, A. I., & Ross, O. A. (2015) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2015.09.011 · Cited by 18 · see citing works
Self-citation
- Authors
- Kouri, N., Ross, O. A., Dombroski, B., Younkin, C. S., Serie, D. J., Soto-Ortolaza, A., Baker, M., Finch, N. C. A., Yoon, H., Kim, J., Fujioka, S., McLean, C. A., Ghetti, B., Spina, S., Cantwell, L. B., Farlow, M. R., Grafman, J., Huey, E. D., Ryung Han, M., Beecher, S., Geller, E. T., Kretzschmar, H. A., Roeber, S., Gearing, M., Juncos, J. L., Vonsattel, J. P. G., Van Deerlin, V. M., Grossman, M., Hurtig, H. I., Gross, R. G., Arnold, S. E., Trojanowski, J. Q., Lee, V. M., Wenning, G. K., White, C. L., Höglinger, G. U., Müller, U., Devlin, B., Golbe, L. I., Crook, J., Parisi, J. E., Boeve, B. F., Josephs, K. A., Wszolek, Z. K., Uitti, R. J., Graff-Radford, N. R., Litvan, I., Younkin, S. G., Wang, L.-S., Ertekin-Taner, N., Rademakers, R., Hakonarsen, H., Schellenberg, G. D., & Dickson, D. W.
- Affiliations
- Mayo Clinic (US)
- University of Pennsylvania (US)
- Mayo Clinic in Florida (US)
- Mental Health Research Institute (AU)
- Indiana University Indianapolis (US)
- Northwestern University (US)
- Columbia University (US)
- Institut für Neuropathologie (DE)
- Emory University (US)
- University of Pennsylvania Health System (US)
- Innsbruck Medical University (AT)
- The University of Texas Southwestern Medical Center (US)
- Philipps University of Marburg (DE)
- Justus-Liebig-Universität Gießen (DE)
- University of Pittsburgh (US)
- Rutgers, The State University of New Jersey (US)
- University of California San Diego (US)
- Children's Hospital of Philadelphia (US)
- Corresponding author
- Kouri, Naomi
- Dickson, Dennis W.
- ORCID
- Kouri, Naomi
- Dombroski, Beth
- Baker, Matthew
- Yoon, Hyejin
- Kim, Jungsu
- Fujioka, Shinsuke
- McLean, Catriona A.
- Ghetti, Bernardino
- Spina, Salvatore
- Farlow, Martin R.
- Grafman, Jordan
- Huey, Edward D.
- Geller, Evan T.
- Gearing, Marla
- Van Deerlin, Vivianna M.
- Grossman, Murray
- Arnold, Steven E.
- Trojanowski, John Q.
- Wenning, Gregor K.
- White, Charles L.
- Höglinger, Günter U.
- Devlin, Bernie
- Golbe, Lawrence I.
- Crook, Julia
- Boeve, Bradley F.
- Josephs, Keith A.
- Uitti, Ryan J.
- Litvan, Irene
- Rademakers, Rosa
- Schellenberg, Gerard D.
- Dickson, Dennis W.
- Venue
- Nature Communications
- Published
- 2015-06-16
- Volume
- 6
- Issue
- 1
- Pages
- 7247-7247
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4469997
- OpenAlex
- W2261318990
- Semantic Scholar
- 25c8836b396f3b56873e619674d9d482cb9d5882
- Cited by
- 219
- References
- 38
- Citations by year
- 2026: 2 · 2025: 17 · 2024: 25 · 2023: 15 · 2022: 25 · 2021: 29 · 2020: 16 · 2019: 25 · 2018: 20 · 2017: 26 · 2016: 13 · 2015: 5
- FWCI
- 12.95
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- PubMed Central (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- DZNE Pub (submittedVersion, other-oa)
- IUScholarWorks (Indiana University) (submittedVersion, cc-by)
- Purdue University Indianapolis (Indiana University) (submittedVersion, cc-by)
- Publisher
- Funders
- Michael J. Fox Foundation for Parkinson's Research (R01 NS078086, P50 NS072187, NS078086)
- Mayo Clinic (P50 NS072187, P50 AG016574, R01 AG032990, R01 NS080820)
- GHR Foundation
- Rainwater Charitable Foundation
- Deutsche Forschungsgemeinschaft (HO2402/6‐2, AG10124)
- Bundesministerium für Bildung und Forschung
- National Institutes of Health (AG 10 124, NIH P50, 5p30ag010124-10, 5p50ag025688-15, AG016574, R01-NS080820, P50 AG016574, P50NS072187, NS078086, R01-NS078086, P30‐AG10124, NS53488, P01 AG17586, R01AG037491, AG 17586, AG017586, NIH P30 AG10133, NS072187, AG037491)
- National Institute on Aging (P50 AG0016574, P30AG010133, P30AG10124, P30AG012300, U01 AG046139, R01-AG037491, P01 AG-17586, P30‐AG‐010124, P50‐AG016574, P01AG017586, P50 AG-025688, R01AG032990, P30 AG-10133)
- National Institute of Neurological Disorders and Stroke (P50-NS53488, P50 NS 072187, R01 NS080820, P50NS053488, R01# NS078086, R01 NS076837)
- State of Florida
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- corticobasal degeneration, progressive supranuclear palsy, genetic susceptibility loci, MAPT, MOBP, SOS1, long non-coding RNA, neurodegenerative disease genetics, shared genetic risk
- MeSH terms
- Adult, Aged, Aged, 80 and over, Basal Ganglia Diseases, Cerebral Cortex, Female, Humans, Male, Middle Aged, Myelin Proteins, Supranuclear Palsy, Progressive, Case-Control Studies, Kinesins, tau Proteins, Neurodegenerative Diseases, Polymorphism, Single Nucleotide, SOS1 Protein, Genome-Wide Association Study, Young Adult, RNA, Long Noncoding
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-17.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-17.
Cited sources are checked by gpt-6-sol.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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