The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index.
Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci
Open accessAbstract
We used a collection of 708 prospectively collected autopsied brains to assess the methylation state of the brain's DNA in relation to Alzheimer's disease (AD). We found that the level of methylation at 71 of the 415,848 interrogated CpGs was significantly associated with the burden of AD pathology, including CpGs in the ABCA7 and BIN1 regions, which harbor known AD susceptibility variants. We validated 11 of the differentially methylated regions in an independent set of 117 subjects. Furthermore, we functionally validated these CpG associations and identified the nearby genes whose RNA expression was altered in AD: ANK1, CDH23, DIP2A, RHBDF2, RPL13, SERPINF1 and SERPINF2. Our analyses suggest that these DNA methylation changes may have a role in the onset of AD given that we observed them in presymptomatic subjects and that six of the validated genes connect to a known AD susceptibility gene network.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Alterations of DNA methylation levels have been shown to be involved in many diseases, including AD [19–24].”
From Distinct sex-specific DNA methylation differences in Alzheimer’s disease (2022) · cites this paper as [19]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“DNA methylation is an important epigenetic modification that regulates gene transcription and is known to be involved in AD”
From Sex-specific DNA methylation differences in Alzheimer’s disease pathology (2021) · cites this paper as [18]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Consistent with previous studies [18, 19, 86, 87], we observed the majority of these sex-specific differences were hyper-methylated in samples with AD neuropathology, for which methylation levels increased as the AD Braak stage increased”
From Sex-specific DNA methylation differences in Alzheimer’s disease pathology (2021) · cites this paper as [18]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“dysregulated DNAm has been observed as an early feature of AD neuropathology in the brain [19]”
From Distinct sex-specific DNA methylation differences in Alzheimer’s disease (2022) · cites this paper as [19]
The cited source says what the claim attributes to it.
In the citing paper
“Importantly, alterations of DNA methylation levels have also been implicated in multiple neurological disorders including AD [18–22]”
From Sex-specific DNA methylation differences in Alzheimer’s disease pathology (2021) · cites this paper as [18]
The cited source says what the claim attributes to it.
In the citing paper
“Notably, none of the 14 CpGs detected in our interaction analysis was identified in previous large-scale DNA methylation studies [18–22]”
From Sex-specific DNA methylation differences in Alzheimer’s disease pathology (2021) · cites this paper as [18]
In the citing paper
“These reference epigenomes, combined with other genomics data, have provided functional and causal insights about several human disease (De Jager et al., 2014; Farh et al., 2015; Yao, Tak, Berman, & Farnham, 2014).”
From Integrative Analysis of Multi-omics Data for Discovery and Functional Studies of Complex Human Diseases (2016) · cites this paper as De Jager et al., 2014
In the citing paper
“The most significant GWAS SNP was also a significant eQTL with the same direction of effect as in CMC for FURIN (rs4702: P = 1 × 10−6), CLCN3 (rs10520163: P = 9 × 10−6), and SNAP91 (rs3798869: P = 3 × 10−4); TSNARE1 (rs4129585: P = 0.057) and CNTN4 (rs17194490: P = 0.07) also had alleles in the same direction of effect as in CMC but did not reach significance.”
From Gene expression elucidates functional impact of polygenic risk for schizophrenia (2016) · cites this paper as [26]
In the citing paper
“and two independent genome-wide studies recently identified a differentially methylated region in the ANK1 gene as associated with the burden of AD pathology [198, 199].”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [199]
In the citing paper
“A different study found altered methylation in the BIN1 locus at cg22883290 in relation to neuritic amyloid plaques and a pathologic diagnosis of AD, and this altered methylation pattern was independent of the effect of the rs744373 susceptibility variant [14].”
From BIN1 protein isoforms are differentially expressed in astrocytes, neurons, and microglia: neuronal and astrocyte BIN1 are implicated in tau pathology (2020) · cites this paper as [14]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Adjusting batch effects in microarray expression data using empirical Bayes methods
Johnson, W. E., Li, C., & Rabinovic, A. (2007) · Biostatistics · doi:10.1093/biostatistics/kxj037 · Cited by 8,658
Sperling, R. A., Aisen, P. S., Beckett, L. A., Bennett, D. A., Craft, S., Fagan, A. M., Iwatsubo, T., Jack, C. R., Kaye, J., Montine, T. J., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.003 · Cited by 7,155
Self-citationMeta-Analysis of 74,046 Individuals Identifies 11 New Susceptibility Loci for Alzheimer’s Disease
(EADI), E. A. D. I., Lambert, J.-C., (GERAD), G. A. E. R. I. A. D., Alzheimer's Disease Genetic Consortium (ADGC), (CHARGE), C. F. H. A. A. R. I. G. E., Ibrahim-Verbaas, C. A., Harold, D., Naj, A. C., Sims, R., Bellenguez, C., et al. (2013) · Nature Genetics · doi:10.1038/ng.2802 · Cited by 4,336
Self-citationHarold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.440 · Cited by 3,326
Self-citationChromHMM: automating chromatin-state discovery and characterization
Ernst, J., & Kellis, M. (2012) · Nature Methods · doi:10.1038/nmeth.1906 · Cited by 2,482
Self-citationGenome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease
the European Alzheimer's Disease Initiative Investigators, Lambert, J.-C., Heath, S., Even, G., Campion, D., Sleegers, K., Hiltunen, M., Combarros, O., Zelenika, D., Bullido, M. J., et al. (2009) · Nature Genetics · doi:10.1038/ng.439 · Cited by 2,234
Du, P., Zhang, X., Huang, C.-C., Jafari, N., Kibbe, W. A., Hou, L., & Lin, S. M. (2010) · BMC Bioinformatics · doi:10.1186/1471-2105-11-587 · Cited by 2,136 · cited 2×
“We then performed a refinement step similar to that used in “ iSVA” 52 where for each independent component i ( 1 = i =k ) we created a sub-matrix of the beta values populated only by methylation probes that were significantly associated with component i .”
lumi : a pipeline for processing Illumina microarray
Du, P., Kibbe, W. A., & Lin, S. M. (2008) · Bioinformatics · doi:10.1093/bioinformatics/btn224 · Cited by 2,028
Initiative, T. A. D. N., Hollingworth, P., CHARGE consortium, EADI1 consortium, Harold, D., Sims, R., Gerrish, A., Lambert, J.-C., Carrasquillo, M. M., Abraham, R., et al. (2011) · Nature Genetics · doi:10.1038/ng.803 · Cited by 1,997
Naj, A. C., Jun, G., Beecham, G. W., Wang, L.-S., Vardarajan, B. N., Buros, J., Gallins, P. J., Buxbaum, J. D., Jarvik, G. P., Crane, P. K., et al. (2011) · Nature Genetics · doi:10.1038/ng.801 · Cited by 1,901 · cited 1×
“…in the BIN1 locus (beta=4.44, p=9.00×10 −8 ) and cg02308560 in the ABCA7 locus (beta=3.62, p=2.45×10 −12 ) 19-22 . cg22883290, is located 5 kb from the 5’ end of the BIN1 gene and 92 kb from the index SNP, rs744373, that best captures the genetic association to AD in this region ( Figure 2c ) 19 .”
InfluentialSelf-citationChen, Y. A., Lemire, M., Choufani, S., Butcher, D. T., Grafodatskaya, D., Zanke, B. W., Gallinger, S., Hudson, T. J., & Weksberg, R. (2013) · Epigenetics · doi:10.4161/epi.23470 · Cited by 1,547 · cited 4×
“Many of these probes showed strong association to gender in a recent report that recommends discarding probes in which 47/50 nucleotides match the sex chromosome sequence during sequence alignment using BLAT 49 .”
InfluentialCharting a dynamic DNA methylation landscape of the human genome
Ziller, M. J., Gu, H., Müller, F., Donaghey, J., Tsai, L. T.-Y., Kohlbacher, O., De Jager, P. L., Rosen, E. D., Bennett, D. A., Bernstein, B. E., et al. (2013) · Nature · doi:10.1038/nature12433 · Cited by 1,357 · cited 1×
“Subsequently, CpG methylation calls were made using custom software 57 , excluding duplicate, low quality reads as well as reads with more than 10% mismatches.”
Self-citationNeuropathology of older persons without cognitive impairment from two community-based studies
Bennett, D. A., Schneider, J. A., Arvanitakis, Z., Kelly, J. F., Aggarwal, N. T., Shah, R. C., & Wilson, R. S. (2006) · Neurology · doi:10.1212/01.wnl.0000219668.47116.e6 · Cited by 1,336
Self-citationGenome-wide Analysis of Genetic Loci Associated With Alzheimer Disease
Seshadri, S. (2010) · JAMA · doi:10.1001/jama.2010.574 · Cited by 1,219
BSMAP: whole genome bisulfite sequence MAPping program
Xi, Y., & Li, W. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-232 · Cited by 1,216
Discovery and characterization of chromatin states for systematic annotation of the human genome
Ernst, J., & Kellis, M. (2010) · Nature Biotechnology · doi:10.1038/nbt.1662 · Cited by 1,075 · cited 1×
“Using histone modification profiles and established methods 27 , each 200 bp segment of the genome is annotated as being in one of 11 chromatin states ( Figure 3a ) that capture the transcriptional states and putative regulatory elements found in this tissue.”
Self-citationLiu, Y., Aryee, M. J., Padyukov, L., Fallin, M. D., Hesselberg, E., Rúnarsson, Á. R., Reinius, L. E., Acevedo, N., Taub, M. A., Ronninger, M., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2487 · Cited by 997 · cited 1×
“It is too early to confidently differentiate between three possibilities that could explain these modest but robust changes in methylation that occur in relation to AD pathology: (1) a fraction of the constituent cortical cells are changing, such as activated astrocytes in the vicinity of neuritic plaques that overexp…”
A human phenome-interactome network of protein complexes implicated in genetic disorders
Lage, K., Karlberg, E., Størling, Z. M., Olason, P., Pedersen, A., Rigina, O., Hinsby, A., Tümer, Z., Pociot, F., Tommerup, N., et al. (2007) · Nature Biotechnology · doi:10.1038/nbt1295 · Cited by 973 · cited 1×
“DAPPLE creates direct and indirect networks of connected proteins using evidence of physical interaction from the InWeb database, which contains 169,810 high-confidence pair-wise interactions involving 12,793 proteins 61 .”
The neuropathology of probable Alzheimer disease and mild cognitive impairment
Schneider, J. A., Arvanitakis, Z., Leurgans, S. E., & Bennett, D. A. (2009) · Annals of Neurology · doi:10.1002/ana.21706 · Cited by 935 · cited 1×
“As has been well documented in neuropathological and imaging studies 25,26 , a large fraction of non-impaired, older individuals demonstrate accumulation of amyloid pathology that is asymptomatic.”
Self-citationAn epigenetic blockade of cognitive functions in the neurodegenerating brain
Gräff, J., Rei, D., Guan, J.-S., Wang, W.-Y., Seo, J., Hennig, K. M., Nieland, T. J. F., Fass, D. M., Kao, P. F., Kahn, M., et al. (2012) · Nature · doi:10.1038/nature10849 · Cited by 853 · cited 1×
“The most compelling evidence that the epigenome may influence AD comes from the manipulation of histone deacetylases (HDAC) in model systems of AD and in off-label treatment of AD patients with HDAC inhibitors 4,5 .”
Overview and Findings from the Rush Memory and Aging Project
Bennett, D. A., Schneider, J. A., Buchman, A. S., Barnes, L. L., Boyle, P. A., & Wilson, R. S. (2012) · Current Alzheimer Research · doi:10.2174/156720512801322663 · Cited by 849 · cited 2×
“More detailed information regarding the two cohorts can be found in previously published literature 42,43 .”
Self-citationBell, J. T., Tsai, P.-C., Yang, T.-P., Pidsley, R., Nisbet, J. P., Glass, D., Mangino, M., Zhai, G., Zhang, F., Valdes, A. M., et al. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002629 · Cited by 700
Self-citationMultiple roles of HDAC inhibition in neurodegenerative conditions
Chuang, D.-M., Leng, Y., Marinova, Z., Kim, H.-J., & Chiu, C.-T. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.06.002 · Cited by 676 · cited 1×
“The most compelling evidence that the epigenome may influence AD comes from the manipulation of histone deacetylases (HDAC) in model systems of AD and in off-label treatment of AD patients with HDAC inhibitors 4,5 .”
Overview and Findings from the Religious Orders Study
Bennett, D. A., Schneider, J. A., Arvanitakis, Z., & Wilson, R. S. (2012) · Current Alzheimer Research · doi:10.2174/156720512801322573 · Cited by 656 · cited 2×
“More detailed information regarding the two cohorts can be found in previously published literature 42,43 .”
Self-citationAging effects on DNA methylation modules in human brain and blood tissue
Horvath, S., Zhang, Y., Langfelder, P., Kahn, R. S., Boks, M. P., van Eijk, K. R., van den Berg, L. H., & Ophoff, R. A. (2012) · Genome biology · doi:10.1186/gb-2012-13-10-r97 · Cited by 652 · cited 1×
“8,10-12 In this study, we present the results of a statistically rigorous gene discovery effort to identify regions of the genome that are differentially methylated in relation to the burden of AD neuropathology.”
Quantitative comparison of genome-wide DNA methylation mapping technologies
Bock, C., Tomazou, E. M., Brinkman, A. B., Müller, F., Simmer, F., Gu, H., Jäger, N., Gnirke, A., Stunnenberg, H. G., & Meissner, A. (2010) · Nature Biotechnology · doi:10.1038/nbt.1681 · Cited by 604 · cited 1×
“…data generated from the same brain DNA samples in four of the subjects (two non-impaired and two AD subjects): in these four subjects, we see a very strong correlation (mean r= 0.97) between the estimated levels of methylation generated by the two technologies, consistent with prior reports 15 .”
InfluentialSelf-citationAnalysing and interpreting DNA methylation data
Bock, C. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3273 · Cited by 600 · cited 1×
“While M-values have certain favorable statistical properties relative to β -values, they are less biologically interpretable than β -values 54 .”
Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease
Lunnon, K., Smith, R., Hannon, E., De Jager, P. L., Srivastava, G., Volta, M., Troakes, C., Al-Sarraj, S., Burrage, J., Macdonald, R., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3782 · Cited by 574 · cited 2×
“To further assess the robustness of our results, we evaluated the 71 significantly associated CpGs in an independent collection of 117 subjects with a different quantitative measure of AD pathology (Braak staging) 24 .”
Self-citationGenome-wide Chromatin State Transitions Associated with Developmental and Environmental Cues
Zhu, J., Adli, M., Zou, J., Verstappen, G., Coyne, M. J., Zhang, X., Durham, T., Miri, M., Deshpande, V., Jager, P. L. D., et al. (2013) · Cell · doi:10.1016/j.cell.2012.12.033 · Cited by 551
Self-citationModel-based variance-stabilizing transformation for Illumina microarray data
Lin, S. M., Du, P., Huber, W. K., & Kibbe, W. A. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkm1075 · Cited by 512 · cited 1×
“Raw probe-level expression data exported from Genome Studio software (Illumina Inc.) were preprocessed with background correction, variance stabilizing transformation, quantile normalization and probe filtering using the lumi package of BioConductor 46,47 .”
Age-Specific Epigenetic Drift in Late-Onset Alzheimer's Disease
Wang, S.-C., Oelze, B., & Schumacher, A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002698 · Cited by 471 · cited 1×
“As noted above, we considered, but elected not to include, terms for (1) the proportion of neurons in each sample or (2) surrogate variables that displayed no correlation with available technical or demographic variables.”
Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer’s disease
Cruchaga, C., Karch, C. M., Jin, S. C., Benitez, B. A., Cai, Y., Guerreiro, R., Harari, O., Norton, J., Budde, J., Bertelsen, S., et al. (2014) · Nature · doi:10.1038/nature12825 · Cited by 461
Chouliaras, L., Mastroeni, D., Delvaux, E., Grover, A., Kenis, G., Hof, P. R., Steinbusch, H. W. M., Coleman, P. D., Rutten, B. P. F., & van den Hove, D. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.02.021 · Cited by 442 · cited 1×
“To date, results of epigenomic studies of AD are sometimes conflicting and have not yet returned robust associations 6-9 .”
Rossin, E. J., Lage, K., Raychaudhuri, S., Xavier, R. J., Tatar, D., Benita, Y., Constortium, I. I. B. D. G., Cotsapas, C., & Daly, M. J. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1001273 · Cited by 438
Transcriptional and Epigenetic Dynamics during Specification of Human Embryonic Stem Cells
Gifford, C. A., Ziller, M. J., Gu, H., Trapnell, C., Donaghey, J., Tsankov, A., Shalek, A. K., Kelley, D. R., Shishkin, A. A., Issner, R., et al. (2013) · Cell · doi:10.1016/j.cell.2013.04.037 · Cited by 435 · cited 2×
“Libraries were then purified and run on the Illumina HiSeq2000 using a standard 36 base protocol 55 .”
Self-citationTumor Necrosis Factor Signaling Requires iRhom2 to Promote Trafficking and Activation of TACE
Adrain, C., Zettl, M., Christova, Y., Taylor, N. A., & Freeman, M. (2012) · Science · doi:10.1126/science.1214400 · Cited by 415 · cited 1×
“While little is known on the potential role of ANK1, the connection of RHBDF2 with PTK2B is consistent with the known role of this molecule in myeloid cells: it is necessary for the transport of TNF α converting enzyme (TACE, also called ADAM17 ), which releases TNF α from the cell surface 33 .”
Increased expression of BIN1 mediates Alzheimer genetic risk by modulating tau pathology
GERAD consortium, Chapuis, J., Hansmannel, F., Gistelinck, M., Mounier, A., Van Cauwenberghe, C., Kolen, K. V., Geller, F., Sottejeau, Y., Harold, D., et al. (2013) · Molecular Psychiatry · doi:10.1038/mp.2013.1 · Cited by 407
Guintivano, J., Aryee, M. J., & Kaminsky, Z. A. (2013) · Epigenetics · doi:10.4161/epi.23924 · Cited by 384 · cited 1×
“As discussed in the main text, we used an R package 53 to quantify the proportion of NeuN+ cells (primarily neurons) in each brain sample using DNA methylation data.”
Distinct DNA methylation changes highly correlated with chronological age in the human brain
Hernandez, D. G., Nalls, M. A., Gibbs, J. R., Arepalli, S., van der Brug, M., Chong, S., Moore, M., Longo, D. L., Cookson, M., Traynor, B. J., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddq561 · Cited by 382 · cited 1×
“8,10-12 In this study, we present the results of a statistically rigorous gene discovery effort to identify regions of the genome that are differentially methylated in relation to the burden of AD neuropathology.”
DNA methylation signatures in development and aging of the human prefrontal cortex
Numata, S., Ye, T., Hyde, T. M., Guitart-Navarro, X., Tao, R., Wininger, M., Colantuoni, C., Weinberger, D. R., Kleinman, J. E., & Lipska, B. K. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.12.020 · Cited by 364 · cited 1×
“8,10-12 In this study, we present the results of a statistically rigorous gene discovery effort to identify regions of the genome that are differentially methylated in relation to the burden of AD neuropathology.”
Personalized Epigenomic Signatures That Are Stable Over Time and Covary with Body Mass Index
Feinberg, A. P., Irizarry, R. A., Fradin, D., Aryee, M. J., Murakami, P. N., Aspelund, T., Eiríksdóttir, G., Harris, T. B., Launer, L. J., Gudnason, V. G., et al. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3001262 · Cited by 341
iRhom2 Regulation of TACE Controls TNF-Mediated Protection Against Listeria and Responses to LPS
McIlwain, D. R., Lang, P. A., Maretzky, T., Hamada, K., Ohishi, K., Maney, S. K., Berger, T., Murthy, A., Duncan, G. S., Xu, H. C., et al. (2012) · Science · doi:10.1126/science.1214448 · Cited by 327 · cited 1×
“Absence of RHBDF2 in mice impacts the normal release of TNF α from the cell surface 34 and impairs systemic immune responses to pathogens 35 .”
Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice
Kraft, A. W., Hu, X., Yoon, H., Yan, P., Xiao, Q., Wang, Y., Gil, S. C., Brown, J., Wilhelmsson, U., Restivo, J. L., et al. (2013) · The FASEB Journal · doi:10.1096/fj.12-208660 · Cited by 324
Bakulski, K. M., Dolinoy, D. C., Sartor, M. A., Paulson, H. L., Konen, J. R., Lieberman, A. P., Albin, R. L., Hu, H., & Rozek, L. S. (2012) · Journal of Alzheimer's Disease · doi:10.3233/jad-2012-111223 · Cited by 255
Gene expression profiling in human neurodegenerative disease
Cooper‐Knock, J., Kirby, J., Ferraiuolo, L., Heath, P. R., Rattray, M., & Shaw, P. J. (2012) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.156 · Cited by 229 · cited 1×
“Such cell type adjustment using surrogate markers for different cell types 37-39 are crude analyses but are helpful to begin to assign some of the transcriptional alterations to certain cell types.”
Relation of neuropathology to cognition in persons without cognitive impairment
Bennett, D. A., Wilson, R. S., Boyle, P. A., Buchman, A. S., & Schneider, J. A. (2012) · Annals of Neurology · doi:10.1002/ana.23654 · Cited by 220 · cited 3×
“As in prior publications 17 a quantitative composite score of neuritic plaque burden was then computed for each individual by dividing the subject's raw count in each of the 5 regions by the population standard deviation in that same region, and then taking the average of the standardized counts…”
InfluentialSelf-citationBrain 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 219
Self-citationSimpson, J. E., Ince, P. G., Shaw, P. J., Heath, P. R., Raman, R., Garwood, C. J., Gelsthorpe, C., Baxter, L., Forster, G., Matthews, F. E., et al. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.04.013 · Cited by 197
CR1 is associated with amyloid plaque burden and age‐related cognitive decline
Chibnik, L. B., Shulman, J. M., Leurgans, S. E., Schneider, J. A., Wilson, R. S., Tran, D., Aubin, C., Buchman, A. S., Heward, C. B., Myers, A. J., et al. (2011) · Annals of Neurology · doi:10.1002/ana.22277 · Cited by 174 · cited 1×
“For example, in our subjects, the well-validated CR1 susceptibility allele explains just 1% of variance in NP burden 18 , and all known AD variants and APOE ε 4 account for 13.9% of the variance in NP burden.”
InfluentialSelf-citationNovel late-onset Alzheimer disease loci variants associate with brain gene expression
Allen, M., Zou, F., Chai, H. S., Younkin, C. S., Crook, J. E., Pankratz, V. S., Carrasquillo, M. M., Rowley, C. N., Nair, A., Middha, S., et al. (2012) · Neurology · doi:10.1212/wnl.0b013e3182605801 · Cited by 167 · cited 2×
“Temporal cortex expression levels for the autopsied Mayo Clinic subjects were obtained as part of a recently published brain expression GWAS (eGWAS), where the methodology is described in detail (eGWAS) 44,45 .”
Self-citationiRhom2 controls the substrate selectivity of stimulated ADAM17-dependent ectodomain shedding
Maretzky, T., McIlwain, D. R., Issuree, P. D. A., Li, X., Malapeira, J., Amin, S., Lang, P. A., Mak, T. W., & Blobel, C. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1302553110 · Cited by 163
Genetic Susceptibility for Alzheimer Disease Neuritic Plaque Pathology
Shulman, J. M., Chen, K., Keenan, B. T., Chibnik, L. B., Fleisher, A., Thiyyagura, P., Roontiva, A., Aubin, C., Patsopoulos, N. A., Corneveaux, J. J., et al. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.2815 · Cited by 162 · cited 3×
“23 The replication DNA methylation analysis uses samples of prefrontal cortex (PFC) obtained from 117 individuals archived in the MRC London Neurodegenerative Disease Brain Bank…”
InfluentialSelf-citationEpigenetic Determinants of Healthy and Diseased Brain Aging and Cognition
Akbarian, S., Beeri, M. S., & Haroutunian, V. H. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.1459 · Cited by 96 · cited 1×
“” Nat Neurosci 17 (9) (August 17): 1156–1163.”
Genetic Regulation of α-Synuclein mRNA Expression in Various Human Brain Tissues
Linnertz, C. L., Saucier, L., Ge, D., Cronin, K. D., Burke, J. R., Browndyke, J. N., Hulette, C. M., Welsh-Bohmer, K. A., & Chiba‐Falek, O. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007480 · Cited by 88 · cited 1×
“Such cell type adjustment using surrogate markers for different cell types 37-39 are crude analyses but are helpful to begin to assign some of the transcriptional alterations to certain cell types.”
iRhom2 is required for the secretion of mouse TNFα
Siggs, O. M., Xiao, N., Wang, Y., Shi, H., Tomisato, W., Li, X., Xia, Y., & Beutler, B. (2012) · Blood · doi:10.1182/blood-2012-03-417949 · Cited by 88 · cited 1×
“Absence of RHBDF2 in mice impacts the normal release of TNF α from the cell surface 34 and impairs systemic immune responses to pathogens 35 .”
Alzheimer Disease Susceptibility Loci: Evidence for a Protein Network under Natural Selection
Raj, T., Shulman, J. M., Keenan, B. T., Chibnik, L. B., Evans, D. A., Bennett, D. A., Stranger, B. E., & Jager, P. L. D. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.02.022 · Cited by 84
Self-citationNegash, S., Bennett, D. A., Wilson, R. S., Schneider, J. A., & Arnold, S. E. (2011) · Current Alzheimer Research · doi:10.2174/156720511795745302 · Cited by 79
Self-citationTanaka, M., Murakami, K., Ozaki, S., Imura, Y., Tong, X., Watanabe, T., Sawaki, T., Kawanami, T., Kawabata, D., Fujii, T., et al. (2010) · FEBS Journal · doi:10.1111/j.1742-4658.2010.07816.x · Cited by 76 · cited 1×
“DIP2A may function as a cell surface receptor protein 30 and, given the putative role of PLD3 31 and SORL1 in amyloid processing, its relation to the burden of NP pathology may well be related to a direct effect on amyloid processing.”
Selected Findings from the Religious Orders Study and Rush Memory and Aging Project
Bennett, D. A., Wilson, R. S., Arvanitakis, Z., Boyle, P. A., de Toledo-Morrell, L., & Schneider, J. A. (2012) · Journal of Alzheimer's Disease · doi:10.3233/jad-2012-129007 · Cited by 69
Self-citationRoet, K. C. D., Franssen, E. H. P., de Bree, F. M., Essing, A. H. W., Zijlstra, S.-J. J., Fagoe, N. D., Eggink, H. M., Eggers, R., Smit, A. B., van Kesteren, R. E., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.1002-13.2013 · Cited by 38 · cited 1×
“Interestingly, SERPINF1 mRNA expression is reduced in AD ( Table 2 ), and its knockdown in an in vitro system leads to reduced neurite outgrowth 32 , suggesting one potential effect of this gene.”
Renner, N. A., Sansing, H. A., Inglis, F. M., Mehra, S., Kaushal, D., Lackner, A. A., & MacLean, A. G. (2012) · Journal of Cellular Physiology · doi:10.1002/jcp.24283 · Cited by 35 · cited 1×
“Since GFAP expression is enhanced with astrocyte activation 40,41 , we cannot distinguish whether the alteration of CDH23 RNA expression (and presumably its altered DNA methylation) is caused by an increased number of astrocytes near neuritic plaques, the activation of these astrocytes, or a…”
(2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002078 · Cited by 7
Cited by
Sorted by citations
Integrative analysis of 111 reference human epigenomes
Roadmap Epigenomics Consortium, Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., Kheradpour, P., Zhang, Z., Wang, J., et al. (2015) · Nature · doi:10.1038/nature14248 · Cited by 6,368
Self-citationAging and aging-related diseases: from molecular mechanisms to interventions and treatments
Guo, J., Huang, X., Dou, L., Yan, M., Shen, T., Tang, W., & Li, J. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01251-0 · Cited by 1,976
Editing DNA Methylation in the Mammalian Genome
Liu, X. S., Wu, H., Ji, X., Stelzer, Y., Wu, X., Czauderna, S., Shu, J., Dadon, D., Young, R. A., & Jaenisch, R. (2016) · Cell · doi:10.1016/j.cell.2016.08.056 · Cited by 1,224
“Importantly, these maps have allowed for the identification of differentially methylated regions (DMRs) at base pair resolution during different stages of normal development as well as disease (De Jager et al., 2014; Landau et al., 2014).”
Religious Orders Study and Rush Memory and Aging Project
Bennett, D. A., Buchman, A. S., Boyle, P. A., Barnes, L. L., Wilson, R. S., & Schneider, J. A. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179939 · Cited by 1,260
Self-citationAgeing, neurodegeneration and brain rejuvenation
Wyss-Coray, T. (2016) · Nature · doi:10.1038/nature20411 · Cited by 1,147
Metadata
- Authors
- De Jager, P. L., Srivastava, G., Lunnon, K., Burgess, J., Schalkwyk, L. C., Yu, L., Eaton, M. L., Keenan, B. T., Ernst, J., McCabe, C., Tang, A., Raj, T., Replogle, J., Brodeur, W., Gabriel, S., Chai, H. S., Younkin, C., Younkin, S. G., Zou, F., Szyf, M., Epstein, C. B., Schneider, J. A., Bernstein, B. E., Meissner, A., Ertekin-Taner, N., Chibnik, L. B., Kellis, M., Mill, J., & Bennett, D. A.
- Affiliations
- Broad Institute (US)
- King's College London (GB)
- Mayo Clinic (US)
- Rush University Medical Center (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Bennett, David A
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2014-08-17
- Volume
- 17
- Issue
- 9
- Pages
- 1156-1163
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC4292795
- OpenAlex
- W2074750860
- Cited by
- 956
- References
- 62
- Citations by year
- 2026: 49 · 2025: 77 · 2024: 74 · 2023: 69 · 2022: 82 · 2021: 94 · 2020: 93 · 2019: 94 · 2018: 93 · 2017: 71 · 2016: 84 · 2015: 59 · 2014: 17
- FWCI
- 31.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Open Access at Essex (University of Essex) (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- eScholarship (California Digital Library) (submittedVersion)
- Figshare (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Open Research Exeter (University of Exeter) (submittedVersion)
- Funders
- National Institute on Aging (R01AG017917, P30-AG 10161, K25AG041906, R01AG036039, R01‐AG17917, R01 AG15819, R01AG018023, R01AG036836, U01AG046152, R01-AG18023, AG036039, R01AG036042, R01AG015819, P30AG010161, RC2AG036547, R01AG032990, U01AG046139, RF1AG015819, RF1AG036042, P50AG016574)
- National Human Genome Research Institute (R01HG004037)
- National Institute of Neurological Disorders and Stroke (R01NS080820)
- National Institute of Environmental Health Sciences (U01ES017155)
- National Center for Research Resources (KL2RR024151)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, DNA methylation, ANK1, BIN1, RHBDF2, ABCA7, differentially methylated regions, gene expression, preclinical Alzheimer's disease, epigenome-wide association study
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Amyloidosis, Brain, Carrier Proteins, Female, Humans, Male, Middle Aged, Nuclear Proteins, Ankyrins, CpG Islands, DNA Methylation, Genetic Predisposition to Disease, Tumor Suppressor Proteins, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Genome-Wide Association Study, Protein Interaction Maps
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.
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.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
