CoChat
Sign Up
Cited by 212Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchGenetic Associations and Epidemiology

The role of ABCA7 in Alzheimer’s disease: evidence from genomics, transcriptomics and methylomics

Open access
De Roeck, Arne, Van Broeckhoven, Christine, Sleegers, Kristel·2019·Acta Neuropathologica
DOI 10.1007/s00401-019-01994-1PMC PMC6660495
Open this paper in CoChat — free accountOpen PDF

Abstract

Genome-wide association studies (GWAS) originally identified ATP-binding cassette, sub-family A, member 7 (ABCA7), as a novel risk gene of Alzheimer's disease (AD). Since then, accumulating evidence from in vitro, in vivo, and human-based studies has corroborated and extended this association, promoting ABCA7 as one of the most important risk genes of both early-onset and late-onset AD, harboring both common and rare risk variants with relatively large effect on AD risk. Within this review, we provide a comprehensive assessment of the literature on ABCA7, with a focus on AD-related human -omics studies (e.g. genomics, transcriptomics, and methylomics). In European and African American populations, indirect ABCA7 GWAS associations are explained by expansion of an ABCA7 variable number tandem repeat (VNTR), and a common premature termination codon (PTC) variant, respectively. Rare ABCA7 PTC variants are strongly enriched in AD patients, and some of these have displayed inheritance patterns resembling autosomal dominant AD. In addition, rare missense variants are more frequent in AD patients than healthy controls, whereas a common ABCA7 missense variant may protect from disease. Methylation at several CpG sites in the ABCA7 locus is significantly associated with AD. Furthermore, ABCA7 contains many different isoforms and ABCA7 splicing has been shown to associate with AD. Besides associations with disease status, these genetic and epigenetic ABCA7 markers also showed significant correlations with AD endophenotypes; in particular amyloid deposition and brain morphology. In conclusion, human-based -omics studies provide converging evidence of (partial) ABCA7 loss as an AD pathomechanism, and future studies should make clear if interventions on ABCA7 expression can serve as a valuable therapeutic target for AD.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1007/s00401-019-01994-1

Cites

Statistics

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.

A few free checks a day · papers already verified open instantly · results are public

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 131 · Cited by 212

Research works printed but not linked: 104

  1. [1]Winblad B Amouyel P Andrieu S Ballard C Brayne C Brodaty H Defeating Alzheimer’s disease and other dementias: a priority for European science and society Lancet Neurol 2016 15 455 532 10.1016/S1474-4422(16)00062-4 26987701 · DOI · Paper page
  2. [2]Jack CR Petersen RC Xu YC O’Brien PC Smith GE Ivnik RJ Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment Neurology 1999 52 1397 1403 10.1212/WNL.52.7.1397 10227624 PMC2730146 · DOI · Paper page
  3. [4]Cuyvers E Sleegers K Genetic variations underlying Alzheimer’s disease: evidence from genome-wide association studies and beyond Lancet Neurol 2016 15 857 868 10.1016/S1474-4422(16)00127-7 27302364 · DOI
  4. [5]Abe-Dohmae S Ueda K Yokoyama S ABCA7, a molecule with unknown function FEBS Lett 2006 580 1178 1182 10.1016/j.febslet.2005.12.029 16376881 · DOI
  5. [6]Aikawa T Holm ML Kanekiyo T ABCA7 and pathogenic pathways of Alzheimer’s disease Brain Sci 2018 8 27 10.3390/brainsci8020027 PMC5836046 29401741 · DOI
  6. [7]Li H Karl T Garner B Understanding the function of ABCA7 in Alzheimer’s disease Biochem Soc Trans 2015 43 920 923 10.1042/BST20150105 26517904 · DOI
  7. [8]Tanaka N Abe-Dohmae S Iwamoto N Yokoyama S Roles of ATP-binding cassette transporter A7 in cholesterol homeostasis and host defense system J Atheroscler Thromb 2011 18 274 281 10.5551/jat.6726 21173549 · DOI
  8. [9]Zhao Q-F Wan Y Wang H-F Sun F-R Hao X-K Tan M-S ABCA7 genotypes confer Alzheimer’s disease risk by modulating amyloid-β pathology J Alzheimers Dis 2016 52 693 703 10.3233/JAD-151005 27003212 · DOI
  9. [10]LaFerla FM Green KN Animal models of Alzheimer disease Cold Spring Harb Perspect Med 2012 2 a006320 10.1101/cshperspect.a006320 23002015 PMC3543097 · DOI · Paper page
  10. [11]Kaminski WE Orsó E Diederich W Klucken J Drobnik W Schmitz G Identification of a novel human sterol-sensitive ATP-binding cassette transporter (ABCA7) Biochem Biophys Res Commun 2000 273 532 538 10.1006/bbrc.2000.2954 10873640 · DOI
  11. [12]Dean M Annilo T Evolution of the Atp-binding cassette (Abc) transporter superfamily in vertebrates Ann Rev Genom Hum Genet 2005 6 123 142 10.1146/annurev.genom.6.080604.162122 16124856 · DOI
  12. [13]Berman HM Westbrook J Feng Z Gilliland G Bhat TN Weissig H The protein data bank Nucleic Acids Res 2000 28 235 242 10.1093/nar/28.1.235 10592235 PMC102472 · DOI · Paper page
  13. [14]Kim WS Fitzgerald ML Kang K Okuhira K Bell SA Manning JJ Abca7 null mice retain normal macrophage phosphatidylcholine and cholesterol efflux activity despite alterations in adipose mass and serum cholesterol levels J Biol Chem 2005 280 3989 3995 10.1074/jbc.M412602200 15550377 · DOI
  14. [15]Kim WS Guillemin GJ Glaros EN Lim CK Garner B Quantitation of ATP-binding cassette subfamily—a transporter gene expression in primary human brain cells NeuroReport 2006 17 891 896 10.1097/01.wnr.0000221833.41340.cd 16738483 · DOI
  15. [17]Zhang Y Sloan SA Clarke LE Caneda C Plaza CA Blumenthal PD Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse Neuron 2016 89 37 53 10.1016/j.neuron.2015.11.013 26687838 PMC4707064 · DOI · Paper page
  16. [18]Krzywinski M Schein J Birol I Connors J Gascoyne R Horsman D Circos: an information aesthetic for comparative genomics Genome Res 2009 19 1639 1645 10.1101/gr.092759.109 19541911 PMC2752132 · DOI
  17. [19]Abe-Dohmae S Ikeda Y Matsuo M Hayashi M Okuhira K Ueda K Human ABCA7 supports apolipoprotein-mediated release of cellular cholesterol and phospholipid to generate high density lipoprotein J Biol Chem 2004 279 604 611 10.1074/jbc.M309888200 14570867 · DOI
  18. [20]Hayashi M Abe-Dohmae S Okazaki M Ueda K Yokoyama S Heterogeneity of high density lipoprotein generated by ABCA1 and ABCA7 J Lipid Res 2005 46 1703 1711 10.1194/jlr.M500092-JLR200 15930518 · DOI
  19. [21]Linsel-Nitschke P Jehle AW Shan J Cao G Bacic D Lan D Potential role of ABCA7 in cellular lipid efflux to apoA-I J Lipid Res 2005 46 86 92 10.1194/jlr.M400247-JLR200 15520449 · DOI
  20. [22]Wang N Lan D Gerbod-Giannone M Linsel-Nitschke P Jehle AW Chen W ATP-binding cassette transporter A7 (ABCA7) binds apolipoprotein A-I and mediates cellular phospholipid but not cholesterol efflux J Biol Chem 2003 278 42906 42912 10.1074/jbc.M307831200 12917409 · DOI
  21. [23]Iwamoto N Abe-Dohmae S Sato R Yokoyama S ABCA7 expression is regulated by cellular cholesterol through the SREBP2 pathway and associated with phagocytosis J Lipid Res 2006 47 1915 1927 10.1194/jlr.M600127-JLR200 16788211 · DOI
  22. [24]Sakae N Liu C-C Shinohara M Frisch-Daiello J Ma L Yamazaki Y ABCA7 deficiency accelerates amyloid-beta generation and Alzheimer’s neuronal pathology J Neurosci 2016 36 3848 3859 10.1523/JNEUROSCI.3757-15.2016 27030769 PMC4812140 · DOI
  23. [25]Nowyhed HN Chandra S Kiosses W Marcovecchio P Andary F Zhao M ATP binding cassette transporter ABCA7 regulates NKT cell development and function by controlling CD1d expression and lipid raft content Sci Rep 2017 7 1 12 10.1038/srep40273 28091533 PMC5238393 · DOI
  24. [26]Wu YC Horvitz HR The C. elegans cell corpse engulfment gene ced-7 encodes a protein similar to ABC transporters Cell 1998 93 951 960 10.1016/S0092-8674(00)81201-5 9635425 · DOI
  25. [27]Tanaka N Abe-Dohmae S Iwamoto N Fitzgerald ML Yokoyama S Helical apolipoproteins of high-density lipoprotein enhance phagocytosis by stabilizing ATP-binding cassette transporter A7 J Lipid Res 2010 51 2591 2599 10.1194/jlr.M006049 20495215 PMC2918442 · DOI
  26. [28]Fu Y Hsiao J-HT Paxinos G Halliday GM Kim WS ABCA7 mediates phagocytic clearance of amyloid-β in the brain J Alzheimers Dis 2016 54 569 584 10.3233/JAD-160456 27472885 · DOI
  27. [29]Kim WS Li H Ruberu K Chan S Elliott DA Low JK Deletion of Abca7 increases cerebral amyloid-β accumulation in the J20 mouse model of Alzheimer’s disease J Neurosci 2013 33 4387 4394 10.1523/JNEUROSCI.4165-12.2013 23467355 PMC6704948 · DOI
  28. [31]Lamartinière Y Boucau M-C Dehouck L Krohn M Pahnke J Candela P ABCA7 downregulation modifies cellular cholesterol homeostasis and decreases amyloid-β peptide efflux in an in vitro model of the blood-brain barrier J Alzheimer’s Dis 2018 64 1 17 10.3233/jad-170883 30010117 · DOI · Paper page
  29. [32]Satoh K Abe-Dohmae S Yokoyama S George-Hyslop P Fraser PE ATP-binding cassette transporter A7 (ABCA7) loss of function alters Alzheimer amyloid processing J Biol Chem 2015 290 24152 24165 10.1074/jbc.m115.655076 26260791 PMC4591804 · DOI · Paper page
  30. [33]Logge W Cheng D Chesworth R Bhatia S Garner B Kim WS Role of Abca7 in mouse behaviours relevant to neurodegenerative diseases PLoS One 2012 7 e45959 10.1371/journal.pone.0045959 23029339 PMC3454356 · DOI
  31. [35]Hollingworth P Harold D Sims R Gerrish A Lambert J-C Carrasquillo MM Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease Nat Genet 2011 43 429 435 10.1038/ng.803 21460840 PMC3084173 · DOI · Paper page
  32. [36]Lambert J-C Heath S Even G Campion D Sleegers K Hiltunen M Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease Nat Genet 2009 41 1094 1099 10.1038/ng.439 19734903 · DOI · Paper page
  33. [39]Reitz C Wang L Lin C Larson EB Graff-radford NR Evans D Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E and the risk of late-onset Alzheimer disease in African Americans JAMA 2013 309 1483 1492 10.1001/jama.2013.2973 23571587 PMC3667653 · DOI · Paper page
  34. [40]Seshadri S Fitzpatrick AL Ikram MA DeStefano AL Gudnason V Boada M Genome-wide analysis of genetic loci associated with Alzheimer disease JAMA 2010 303 1832 1840 10.1001/jama.2010.574 20460622 PMC2989531 · DOI · Paper page
  35. [41]Rentzsch P Witten D Cooper GM Shendure J Kircher M CADD: predicting the deleteriousness of variants throughout the human genome Nucleic Acids Res 2018 47 1 9 10.1093/nar/gky1016 PMC6323892 30371827 · DOI · Paper page
  36. [42]Machiela MJ Chanock SJ LDlink: a web-based application for exploring population-specific haplotype structure and linking correlated alleles of possible functional variants Bioinformatics 2015 31 3555 3557 10.1093/bioinformatics/btv402 26139635 PMC4626747 · DOI · Paper page
  37. [43]Almeida JFF dos Santos LR Trancozo M de Paula F Updated meta-analysis of BIN1, CR1, MS4A6A, CLU, and ABCA7 variants in Alzheimer’s disease J Mol Neurosci 2018 64 471 477 10.1007/s12031-018-1045-y 29504051 · DOI
  38. [44]Shulman JM Chen K Keenan BT Chibnik LB Fleisher A Thiyyagura P Genetic susceptibility for Alzheimer disease neuritic plaque pathology JAMA Neurol 2013 70 1150 1157 10.1001/jamaneurol.2013.2815 23836404 PMC3773291 · DOI
  39. [45]Hughes TM Lopez OL Evans RW Kamboh MI Williamson JD Klunk WE Markers of cholesterol transport are associated with amyloid deposition in the brain Neurobiol Aging 2014 35 802 807 10.1016/j.neurobiolaging.2013.09.040 24199960 PMC3896052 · DOI
  40. [46]Apostolova LG Risacher SL Duran T Stage EC Goukasian N West JD Associations of the top 20 Alzheimer disease risk variants with brain amyloidosis JAMA Neurol 2018 75 328 341 10.1001/jamaneurol.2017.4198 29340569 PMC5885860 · DOI
  41. [47]Ma F Zong Y Wang H Li J Cao X Tan L ABCA7 genotype altered Aβ levels in cerebrospinal fluid in Alzheimer’s disease without dementia Ann Transl Med 2018 6 437 10.21037/atm.2018.07.04 30596067 PMC6281527 · DOI
  42. [48]Ramirez LM Goukasian N Porat S Hwang KS Eastman JA Hurtz S Common variants in ABCA7 and MS4A6A are associated with cortical and hippocampal atrophy Neurobiol Aging 2016 39 82 89 10.1016/j.neurobiolaging.2015.10.037 26923404 · DOI
  43. [49]Roshchupkin GV Adams HH van der Lee SJ Vernooij MW van Duijn CM Uitterlinden AG Fine-mapping the effects of Alzheimer’s disease risk loci on brain morphology Neurobiol Aging 2016 48 204 211 10.1016/j.neurobiolaging.2016.08.024 27718423 · DOI
  44. [50]Stage E Duran T Risacher SL Goukasian N Do TM West JD The effect of the top 20 Alzheimer disease risk genes on gray-matter density and FDG PET brain metabolism Alzheimer’s Dement Diagn, Assess Dis Monit 2016 5 53 66 10.1016/j.dadm.2016.12.003 PMC5198883 28054028 · DOI
  45. [51]Sinha N Reagh ZM Tustison NJ Berg CN Shaw A Myers CE ABCA7 risk variant in healthy older African Americans is associated with a functionally isolated entorhinal cortex mediating deficient generalization of prior discrimination training Hippocampus 2018 10.1002/hipo.23042 30318785 PMC6462424 · DOI
  46. [52]Wachinger C Nho K Saykin AJ Reuter M Rieckmann A A longitudinal imaging genetics study of neuroanatomical asymmetry in Alzheimer’s disease Biol Psychiatry 2018 84 522 530 10.1016/j.biopsych.2018.04.017 29885764 PMC6123250 · DOI
  47. [53]Karch CM Jeng AT Nowotny P Cady J Cruchaga C Goate AM Expression of novel Alzheimer’s disease risk genes in control and Alzheimer’s disease brains PLoS One 2012 7 e50976 10.1371/journal.pone.0050976 23226438 PMC3511432 · DOI · Paper page
  48. [54]Engelman CD Koscik RL Jonaitis EM Okonkwo OC Hermann BP La Rue A Interaction between two cholesterol metabolism genes influences memory: findings from the Wisconsin registry for Alzheimer’s prevention J Alzheimer’s Dis 2013 36 749 757 10.3233/JAD-130482 23669301 PMC3759032 · DOI
  49. [55]Carrasquillo MM Khan QUA Murray ME Krishnan S Aakre J Pankratz VS Late-onset Alzheimer disease genetic variants in posterior cortical atrophy and posterior AD Neurology 2014 82 1455 1462 10.1212/WNL.0000000000000335 24670887 PMC4001196 · DOI
  50. [56]Carrasquillo MM Crook JE Pedraza O Thomas CS Pankratz VS Allen M Late-onset Alzheimer’s risk variants in memory decline, incident mild cognitive impairment, and Alzheimer’s disease Neurobiol Aging 2015 36 60 67 10.1016/j.neurobiolaging.2014.07.042 25189118 PMC4268433 · DOI
  51. [57]Nettiksimmons J Tranah G Evans DS Yokoyama JS Yaffe K Gene-based aggregate SNP associations between candidate AD genes and cognitive decline Age (Omaha) 2016 38 41 10.1007/s11357-016-9885-2 PMC5005889 27005436 · DOI
  52. [58]Schott JM Crutch SJ Carrasquillo MM Uphill J Shakespeare TJ Ryan NS Genetic risk factors for the posterior cortical atrophy variant of Alzheimer’s disease Alzheimer’s Dement 2016 12 862 871 10.1016/j.jalz.2016.01.010 26993346 PMC4982482 · DOI
  53. [59]Andrews SJ Das D Anstey KJ Easteal S Late onset Alzheimer’s disease risk variants in cognitive decline: the PATH through life study J Alzheimers Dis 2017 57 423 436 10.3233/JAD-160774 28269768 · DOI
  54. [60]Monsell SE Mock C Fardo DW Bertelsen S Cairns NJ Roe CM Genetic comparison of symptomatic and asymptomatic persons with Alzheimer disease neuropathology Alzheimer Dis Assoc Disord 2017 31 232 238 10.1097/WAD.0000000000000179 27849641 PMC5432419 · DOI
  55. [61]Hohman TJ Koran ME Thornton-Wells T Alzheimer’s Neuroimaging Initiative Epistatic genetic effects among Alzheimer’s candidate genes PLoS One 2013 8 e80839 10.1371/journal.pone.0080839 24260488 PMC3832488 · DOI
  56. [62]Frisoni GB Fox NC Jack CR Scheltens P Thompson PM The clinical use of structural MRI in Alzheimer disease Nat Rev Neurol 2010 6 67 77 10.1038/nrneurol.2009.215 20139996 PMC2938772 · DOI · Paper page
  57. [63]Vivot A Glymour MM Tzourio C Amouyel P Chêne G Dufouil C Association of Alzheimer’s related genotypes with cognitive decline in multiple domains: results from the three-city Dijon study Mol Psychiatry 2015 20 1173 1178 10.1038/mp.2015.62 26033242 · DOI
  58. [64]Ober C Vercelli D Gene-environment interactions in human disease: nuisance or opportunity? Trends Genet 2011 27 107 115 10.1016/j.tig.2010.12.004 21216485 PMC3073697 · DOI
  59. [65]Crutch SJ Lehmann M Schott JM Rabinovici GD Rossor MN Fox NC Posterior cortical atrophy Lancet Neurol 2012 11 170 178 10.1016/S1474-4422(11)70289-7 22265212 PMC3740271 · DOI
  60. [66]Logue MW Schu M Vardarajan BN Farrell J Lunetta KL Jun G Search for age-related macular degeneration risk variants in Alzheimer disease genes and pathways Neurobiol Aging 2014 35 1510.e7 1510.e18 10.1016/j.neurobiolaging.2013.12.007 PMC3961547 24439028 · DOI
  61. [67]Kjeldsen EW Tybjærg-Hansen A Nordestgaard BG Frikke-Schmidt R ABCA7 and risk of dementia and vascular disease in the Danish population Ann Clin Transl Neurol 2018 5 41 51 10.1002/acn3.506 29376091 PMC5771325 · DOI
  62. [68]Vasquez JB Fardo DW Estus S ABCA7 expression is associated with Alzheimer’s disease polymorphism and disease status Neurosci Lett 2013 556 58 62 10.1016/j.neulet.2013.09.058 24141082 PMC3863933 · DOI · Paper page
  63. [69]Allen M Zou F Chai HS Younkin CS Crook J Pankratz VS Novel late-onset Alzheimer disease loci variants associate with brain gene expression Neurology 2012 79 221 228 10.1212/WNL.0b013e3182605801 22722634 PMC3398432 · DOI
  64. [70]Bamji-Mirza M Li Y Najem D Liu QY Walker D Lue L-F Genetic variations in ABCA7 can increase secreted levels of amyloid-β40 and amyloid-β42 peptides and ABCA7 transcription in cell culture models J Alzheimer’s Dis 2016 53 875 892 10.3233/JAD-150965 27314524 · DOI
  65. [74]De Roeck A, De Coster W, Bossaerts L, Cacace R, De Pooter T, Van Dongen J, et al. (2018) Accurate characterization of expanded tandem repeat length and sequence through whole genome long-read sequencing on PromethION. bioRxiv. 10.1101/439026 PMC6857246 31727106 · DOI
  66. [76]Logue MW Lancour D Farrell J Simkina I Fallin MD Lunetta KL Targeted sequencing of Alzheimer disease genes in African Americans implicates novel risk variants Front Neurosci 2018 12 1 11 10.3389/fnins.2018.00592 30210277 PMC6119822 · DOI
  67. [77]Steinberg S Stefansson H Jonsson T Johannsdottir H Ingason A Helgason H Loss-of-function variants in ABCA7 confer risk of Alzheimer’s disease Nat Genet 2015 47 445 447 10.1038/ng.3246 25807283 · DOI · Paper page
  68. [78]Chen JA Wang Q Davis-Turak J Li Y Karydas AM Hsu SC A multiancestral genome-wide exome array study of Alzheimer Disease, frontotemporal dementia, and progressive supranuclear palsy JAMA Neurol 2015 72 414 422 10.1001/jamaneurol.2014.4040 25706306 PMC4397175 · DOI
  69. [80]Allen M Lincoln SJ Corda M Watzlawik JO Carrasquillo MM Reddy JS ABCA7 loss-of-function variants, expression, and neurologic disease risk Neurol Genet 2017 3 e126 10.1212/NXG.0000000000000126 28097223 PMC5217615 · DOI
  70. [82]Del-Aguila JL Fernández MV Jimenez J Black K Ma S Deming Y Role of ABCA7 loss-of-function variant in Alzheimer’s disease: a replication study in European-Americans Alzheimers Res Ther 2015 7 73 10.1186/s13195-015-0154-x 26654793 PMC4675010 · DOI
  71. [84]Patel T Brookes KJ Turton J Chaudhury S Guetta-Baranes T Guerreiro R Whole-exome sequencing of the BDR cohort: evidence to support the role of the PILRA gene in Alzheimer’s disease Neuropathol Appl Neurobiol 2018 44 506 521 10.1111/nan.12452 29181857 PMC6005734 · DOI
  72. [86]Sassi C Nalls MA Ridge PG Gibbs JR Ding J Lupton MK ABCA7 p. G215S as potential protective factor for Alzheimer’s disease Neurobiol Aging 2016 46 235.e1 235.e9 10.1016/j.neurobiolaging.2016.04.004 PMC5024078 27289440 · DOI
  73. [89]Vasquez JB Simpson JF Harpole R Estus S Alzheimer’s disease genetics and ABCA7 splicing J Alzheimers Dis 2017 59 633 641 10.3233/JAD-170872 28655137 PMC5890296 · DOI
  74. [90]Lek M Karczewski KJ Minikel EV Samocha KE Banks E Fennell T Analysis of protein-coding genetic variation in 60,706 humans Nature 2016 536 285 291 10.1038/nature19057 27535533 PMC5018207 · DOI · Paper page
  75. [92]Van den Bossche T Sleegers K Cuyvers E Engelborghs S Sieben A De Roeck A Phenotypic characteristics of Alzheimer patients carrying an ABCA7 mutation Neurology 2016 86 2126 2133 10.1212/WNL.0000000000002628 27037232 PMC4917260 · DOI
  76. [93]May P Pichler S Hartl D Bobbili DR Mayhaus M Spaniol C Rare ABCA7 variants in 2 German families with Alzheimer disease Neurol Genet 2018 4 e224 10.1212/NXG.0000000000000224 29577078 PMC5863691 · DOI · Paper page
  77. [94]Nuytemans K Maldonado L Ali A John-Williams K Beecham GW Martin E Overlap between Parkinson disease and Alzheimer disease in ABCA7 functional variants Neurol Genet 2016 2 e44 10.1212/NXG.0000000000000044 27066581 PMC4817903 · DOI
  78. [96]Hansson O Zetterberg H Vanmechelen E Vanderstichele H Andreasson U Londos E Evaluation of plasma Aβ40and Aβ42as predictors of conversion to Alzheimer’s disease in patients with mild cognitive impairment Neurobiol Aging 2010 31 357 367 10.1016/j.neurobiolaging.2008.03.027 18486992 · DOI
  79. [97]Lee S Emond MJ Bamshad MJ Barnes KC Rieder MJ Nickerson DA Optimal unified approach for rare-variant association testing with application to small-sample case-control whole-exome sequencing studies Am J Hum Genet 2012 91 224 237 10.1016/j.ajhg.2012.06.007 22863193 PMC3415556 · DOI
  80. [98]Jones PA Functions of DNA methylation: islands, start sites, gene bodies and beyond Nat Rev Genet 2012 13 484 492 10.1038/nrg3230 22641018 · DOI · Paper page
  81. [100]Yu L Chibnik LB Srivastava GP Pochet N Yang J Xu J Association of brain DNA methylation in SORL1, ABCA7, HLA-DRB5, SLC24A4, and BIN1 With pathological diagnosis of Alzheimer disease JAMA Neurol 2015 72 1 15 24 10.1001/jamaneurol.2014.3049 25365775 PMC4344367 · DOI · Paper page
  82. [101]Chibnik LB Yu L Eaton ML Srivastava G Schneider JA Kellis M Alzheimer’s loci: epigenetic associations and interaction with genetic factors Ann Clin Transl Neurol 2015 2 636 647 10.1002/acn3.201 26125039 PMC4479524 · DOI · Paper page
  83. [102]Reddington JP Perricone SM Nestor CE Reichmann J Youngson NA Suzuki M Redistribution of H3K27me3 upon DNA hypomethylation results in de-repression of Polycomb target genes Genome Biol 2013 15 45 10.1186/gb-2013-14-3-r25 PMC4053768 23531360 · DOI · Paper page
  84. [103]Humphries C Kohli MA Whitehead P Mash DC Pericak-Vance MA Gilbert J Alzheimer disease (AD) specific transcription, DNA methylation and splicing in twenty AD associated loci Mol Cell Neurosci 2015 67 37 45 10.1016/j.mcn.2015.05.003 26004081 PMC4540636 · DOI
  85. [105]Yamazaki K Yoshino Y Mori T Yoshida T Ozaki Y Sao T Gene expression and methylation analysis of ABCA7 in patients with Alzheimer’s disease J Alzheimers Dis 2017 57 171 181 10.3233/JAD-161195 28222527 · DOI
  86. [106]Ikeda Y Abe-Dohmae S Munehira Y Aoki R Kawamoto S Furuya A Posttranscriptional regulation of human ABCA7 and its function for the apoA-I-dependent lipid release Biochem Biophys Res Commun 2003 311 313 318 10.1016/j.bbrc.2003.10.002 14592415 · DOI
  87. [107]Frankish A Diekhans M Ferreira A-M Johnson R Jungreis I Loveland J GENCODE reference annotation for the human and mouse genomes Nucleic Acids Res 2018 47 766 773 10.1093/nar/gky955 PMC6323946 30357393 · DOI
  88. [108]Raj T Li YI Wong G Humphrey J Wang M Ramdhani S Integrative transcriptome analyses of the aging brain implicate altered splicing in Alzheimer’s disease susceptibility Nat Genet 2018 50 1584 1592 10.1038/s41588-018-0238-1 30297968 PMC6354244 · DOI
  89. [110]Elsnerova K Bartakova A Tihlarik J Bouda J Rob L Skapa P Gene expression profiling reveals novel candidate markers of ovarian carcinoma intraperitoneal metastasis J Cancer 2017 8 3598 3606 10.7150/jca.20766 29151946 PMC5687176 · DOI
  90. [111]Liu X Li Q Zhou J Zhang S ATP-binding cassette transporter A7 accelerates epithelial-to-mesenchymal transition in ovarian cancer cells by upregulating the transforming growth factor-β signaling pathway Oncol Lett 2018 16 5868 5874 10.3892/ol.2018.9366 30333865 PMC6176408 · DOI
  91. [112]Mohelnikova-Duchonova B Brynychova V Oliverius M Honsova E Kala Z Muckova K Differences in transcript levels of ABC transporters between pancreatic adenocarcinoma and nonneoplastic tissues Pancreas 2013 42 707 716 10.1097/MPA.0b013e318279b861 23462326 · DOI
  92. [113]Heimerl S Bosserhoff AK Langmann T Ecker J Schmitz G Mapping ATP-binding cassette transporter gene expression profiles in melanocytes and melanoma cells Melanoma Res 2007 17 265 273 10.1097/CMR.0b013e3282a7e0b9 17885581 · DOI
  93. [114]Tabarés-Seisdedos R Rubenstein JL Inverse cancer comorbidity: a serendipitous opportunity to gain insight into CNS disorders Nat Rev Neurosci 2013 14 293 304 10.1038/nrn3464 23511909 · DOI
  94. [115]Ibáñez K Boullosa C Tabarés-Seisdedos R Baudot A Valencia A Molecular evidence for the inverse comorbidity between central nervous system disorders and cancers detected by transcriptomic meta-analyses PLoS Genet 2014 10 1 7 10.1371/journal.pgen.1004173 PMC3930576 24586201 · DOI
  95. [116]Feng YCA Cho K Lindström S Kraft P Cormack J Blalock K Investigating the genetic relationship between Alzheimer’s disease and cancer using GWAS summary statistics Hum Genet 2017 136 1341 1351 10.1007/s00439-017-1831-6 28780673 PMC5693762 · DOI
  96. [117]Witte JS Visscher PM Wray NR The contribution of genetic variants to disease depends on the ruler Nat Publ Gr 2014 15 765 776 10.1038/nrg3786 PMC4412738 25223781 · DOI
  97. [118]Patel H, Dobson RJB, Newhouse SJ (2019) Meta-analysis of Alzheimer’s disease brain transcriptomic data. bioRxiv. 10.1101/480459 PMC6484273 30909231 · DOI
  98. [119]Grindberg RV Yee-Greenbaum JL McConnell MJ Novotny M O’Shaughnessy AL Lambert GM RNA-sequencing from single nuclei Proc Natl Acad Sci 2013 110 19802 19807 10.1073/pnas.1319700110 24248345 PMC3856806 · DOI · Paper page
  99. [121]Garalde DR Snell EA Jachimowicz D Sipos B Lloyd JH Bruce M Highly parallel direct RNA sequencing on an array of nanopores Nat Methods 2018 15 201 206 10.1038/nmeth.4577 29334379 · DOI
  100. [122]Rhoads A Au KF PacBio sequencing and its applications Genom, Proteom Bioinforma 2015 13 278 289 10.1016/j.gpb.2015.08.002 PMC4678779 26542840 · DOI
  101. [123]Jones VC Atkinson-Dell R Verkhratsky A Mohamet L Aberrant iPSC-derived human astrocytes in Alzheimer’s disease Cell Death Dis 2017 8 1 11 10.1038/cddis.2017.89 28333144 PMC5386580 · DOI · Paper page
  102. [124]Kelava I Lancaster MA Dishing out mini-brains: current progress and future prospects in brain organoid research Dev Biol 2016 420 199 209 10.1016/j.ydbio.2016.06.037 27402594 PMC5161139 · DOI
  103. [125]Qian H Zhao X Cao P Lei J Yan N Gong X Structure of the human lipid exporter ABCA1 Cell 2017 10.1016/j.cell.2017.05.020 28602350 · DOI
  104. [126]Watson M Warr A Errors in long-read assemblies can critically affect protein prediction Nat Biotechnol 2019 15 1 3 10.1038/s41587-018-0004-z 30670796 · DOI

Authors
De Roeck, A., Van Broeckhoven, C., & Sleegers, K.
Affiliations
University of Antwerp (BE)
Corresponding author
Sleegers, Kristel
ORCID
Sleegers, Kristel
Venue
Acta Neuropathologica
Publisher
Springer Science and Business Media LLC
Published
2019-03-22
Volume
138
Issue
2
Pages
201-220
ISSN
  • 0001-6322 (ISSN-L)
  • 1432-0533
DOI
10.1007/s00401-019-01994-1
PMC
PMC6660495
OpenAlex
W2936160979
Cited by
212
References
131
Citations by year
2026: 16 · 2025: 32 · 2024: 36 · 2023: 33 · 2022: 33 · 2021: 38 · 2020: 18 · 2019: 5
FWCI
2.77
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Neuropathologica (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Fonds Wetenschappelijk Onderzoek
  • Universiteit Antwerpen
  • Vlaamse regering
  • Fondation pour la Recherche sur Alzheimer
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
ABCA7, Alzheimer's disease, genetic risk variants, variable number tandem repeats, rare missense variants, autosomal dominant inheritance, DNA methylation, CpG sites, alternative splicing, amyloid deposition, brain structure, endophenotypes, therapeutic target
MeSH terms
Alzheimer Disease, Amyloid, Animals, Atrophy, Brain, Cognition, Disease Models, Animal, Ethnicity, Female, Genes, Dominant, Humans, Male, Risk, Codon, Nonsense, ATP-Binding Cassette Transporters, Minisatellite Repeats, CpG Islands, DNA Methylation, Genetic Predisposition to Disease, Mutation, Missense, Polymorphism, Single Nucleotide, Genomics, Lipid Metabolism, Mice, Transcriptome

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