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Open Access 01-08-2019 | Alzheimer's Disease | Review

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

Authors: Arne De Roeck, Christine Van Broeckhoven, Kristel Sleegers

Published in: Acta Neuropathologica | Issue 2/2019

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.

Winblad B, Amouyel P, Andrieu S, Ballard C, Brayne C, Brodaty H et al (2016) Defeating Alzheimer’s disease and other dementias: a priority for European science and society. Lancet Neurol 15:455–532. https://doi.org/10.1016/S1474-4422(16)00062-4 CrossRefPubMed

Jack CR, Petersen RC, Xu YC, O’Brien PC, Smith GE, Ivnik RJ et al (1999) Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment. Neurology 52:1397–1403. https://doi.org/10.1212/WNL.52.7.1397 CrossRefPubMed

Cacace R, Sleegers K, Van Broeckhoven C (2016) Molecular genetics of early-onset Alzheimer disease revisited. Alzheimer’s Dement 12:733–748. https://doi.org/10.1016/j.jalz.2016.01.012 CrossRef

Cuyvers E, Sleegers K (2016) Genetic variations underlying Alzheimer’s disease: evidence from genome-wide association studies and beyond. Lancet Neurol 15:857–868. https://doi.org/10.1016/S1474-4422(16)00127-7 CrossRefPubMed

Abe-Dohmae S, Ueda K, Yokoyama S (2006) ABCA7, a molecule with unknown function. FEBS Lett 580:1178–1182. https://doi.org/10.1016/j.febslet.2005.12.029 CrossRefPubMed

Aikawa T, Holm ML, Kanekiyo T (2018) ABCA7 and pathogenic pathways of Alzheimer’s disease. Brain Sci 8:27. https://doi.org/10.3390/brainsci8020027 CrossRefPubMedCentral

Li H, Karl T, Garner B (2015) Understanding the function of ABCA7 in Alzheimer’s disease. Biochem Soc Trans 43:920–923. https://doi.org/10.1042/BST20150105 CrossRefPubMed

Tanaka N, Abe-Dohmae S, Iwamoto N, Yokoyama S (2011) Roles of ATP-binding cassette transporter A7 in cholesterol homeostasis and host defense system. J Atheroscler Thromb 18:274–281. https://doi.org/10.5551/jat.6726 CrossRefPubMed

Zhao Q-F, Wan Y, Wang H-F, Sun F-R, Hao X-K, Tan M-S et al (2016) ABCA7 genotypes confer Alzheimer’s disease risk by modulating amyloid-β pathology. J Alzheimers Dis 52:693–703. https://doi.org/10.3233/JAD-151005 CrossRefPubMed

10.

LaFerla FM, Green KN (2012) Animal models of Alzheimer disease. Cold Spring Harb Perspect Med 2:a006320. https://doi.org/10.1101/cshperspect.a006320 CrossRefPubMedPubMedCentral

11.

Kaminski WE, Orsó E, Diederich W, Klucken J, Drobnik W, Schmitz G (2000) Identification of a novel human sterol-sensitive ATP-binding cassette transporter (ABCA7). Biochem Biophys Res Commun 273:532–538. https://doi.org/10.1006/bbrc.2000.2954 CrossRefPubMed

12.

Dean M, Annilo T (2005) Evolution of the Atp-binding cassette (Abc) transporter superfamily in vertebrates. Ann Rev Genom Hum Genet 6:123–142. https://doi.org/10.1146/annurev.genom.6.080604.162122 CrossRef

13.

Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H et al (2000) The protein data bank. Nucleic Acids Res 28:235–242. https://doi.org/10.1093/nar/28.1.235 CrossRefPubMedPubMedCentral

14.

Kim WS, Fitzgerald ML, Kang K, Okuhira K, Bell SA, Manning JJ et al (2005) Abca7 null mice retain normal macrophage phosphatidylcholine and cholesterol efflux activity despite alterations in adipose mass and serum cholesterol levels. J Biol Chem 280:3989–3995. https://doi.org/10.1074/jbc.M412602200 CrossRefPubMed

15.

Kim WS, Guillemin GJ, Glaros EN, Lim CK, Garner B (2006) Quantitation of ATP-binding cassette subfamily—a transporter gene expression in primary human brain cells. NeuroReport 17:891–896. https://doi.org/10.1097/01.wnr.0000221833.41340.cd CrossRefPubMed

16.

Zhang Y, Chen K, Sloan SA, Bennett ML, Scholze AR, O’Keeffe S et al (2014) An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J Neurosci 34:11929–11947. https://doi.org/10.1523/JNEUROSCI.1860-14.2014 CrossRefPubMedPubMedCentral

17.

Zhang Y, Sloan SA, Clarke LE, Caneda C, Plaza CA, Blumenthal PD et al (2016) Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse. Neuron 89:37–53. https://doi.org/10.1016/j.neuron.2015.11.013 CrossRefPubMed

18.

Krzywinski M, Schein J, Birol I, Connors J, Gascoyne R, Horsman D et al (2009) Circos: an information aesthetic for comparative genomics. Genome Res 19:1639–1645. https://doi.org/10.1101/gr.092759.109 CrossRefPubMedPubMedCentral

19.

Abe-Dohmae S, Ikeda Y, Matsuo M, Hayashi M, Okuhira K, Ueda K et al (2004) Human ABCA7 supports apolipoprotein-mediated release of cellular cholesterol and phospholipid to generate high density lipoprotein. J Biol Chem 279:604–611. https://doi.org/10.1074/jbc.M309888200 CrossRefPubMed

20.

Hayashi M, Abe-Dohmae S, Okazaki M, Ueda K, Yokoyama S (2005) Heterogeneity of high density lipoprotein generated by ABCA1 and ABCA7. J Lipid Res 46:1703–1711. https://doi.org/10.1194/jlr.M500092-JLR200 CrossRefPubMed

21.

Linsel-Nitschke P, Jehle AW, Shan J, Cao G, Bacic D, Lan D et al (2005) Potential role of ABCA7 in cellular lipid efflux to apoA-I. J Lipid Res 46:86–92. https://doi.org/10.1194/jlr.M400247-JLR200 CrossRefPubMed

22.

Wang N, Lan D, Gerbod-Giannone M, Linsel-Nitschke P, Jehle AW, Chen W et al (2003) ATP-binding cassette transporter A7 (ABCA7) binds apolipoprotein A-I and mediates cellular phospholipid but not cholesterol efflux. J Biol Chem 278:42906–42912. https://doi.org/10.1074/jbc.M307831200 CrossRefPubMed

23.

Iwamoto N, Abe-Dohmae S, Sato R, Yokoyama S (2006) ABCA7 expression is regulated by cellular cholesterol through the SREBP2 pathway and associated with phagocytosis. J Lipid Res 47:1915–1927. https://doi.org/10.1194/jlr.M600127-JLR200 CrossRefPubMed

24.

Sakae N, Liu C-C, Shinohara M, Frisch-Daiello J, Ma L, Yamazaki Y et al (2016) ABCA7 deficiency accelerates amyloid-beta generation and Alzheimer’s neuronal pathology. J Neurosci 36:3848–3859. https://doi.org/10.1523/JNEUROSCI.3757-15.2016 CrossRefPubMedPubMedCentral

25.

Nowyhed HN, Chandra S, Kiosses W, Marcovecchio P, Andary F, Zhao M et al (2017) ATP binding cassette transporter ABCA7 regulates NKT cell development and function by controlling CD1d expression and lipid raft content. Sci Rep 7:1–12. https://doi.org/10.1038/srep40273 CrossRef

26.

Wu YC, Horvitz HR (1998) The C. elegans cell corpse engulfment gene ced-7 encodes a protein similar to ABC transporters. Cell 93:951–960. https://doi.org/10.1016/S0092-8674(00)81201-5 CrossRefPubMed

27.

Tanaka N, Abe-Dohmae S, Iwamoto N, Fitzgerald ML, Yokoyama S (2010) Helical apolipoproteins of high-density lipoprotein enhance phagocytosis by stabilizing ATP-binding cassette transporter A7. J Lipid Res 51:2591–2599. https://doi.org/10.1194/jlr.M006049 CrossRefPubMedPubMedCentral

28.

Fu Y, Hsiao J-HT, Paxinos G, Halliday GM, Kim WS (2016) ABCA7 mediates phagocytic clearance of amyloid-β in the brain. J Alzheimers Dis 54:569–584. https://doi.org/10.3233/JAD-160456 CrossRefPubMed

29.

Kim WS, Li H, Ruberu K, Chan S, Elliott DA, Low JK et al (2013) Deletion of Abca7 increases cerebral amyloid-β accumulation in the J20 mouse model of Alzheimer’s disease. J Neurosci 33:4387–4394. https://doi.org/10.1523/JNEUROSCI.4165-12.2013 CrossRefPubMedPubMedCentral

30.

Kanekiyo T, Bu G (2014) The low-density lipoprotein receptor-related protein 1 and amyloid-β clearance in Alzheimer’s disease. Front Aging Neurosci 6:1–12. https://doi.org/10.3389/fnagi.2014.00093 CrossRef

31.

Lamartinière Y, Boucau M-C, Dehouck L, Krohn M, Pahnke J, Candela P et al (2018) 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 64:1–17. https://doi.org/10.3233/jad-170883 CrossRef

32.

Satoh K, Abe-Dohmae S, Yokoyama S, George-Hyslop P, Fraser PE (2015) ATP-binding cassette transporter A7 (ABCA7) loss of function alters Alzheimer amyloid processing. J Biol Chem 290:24152–24165. https://doi.org/10.1074/jbc.m115.655076 CrossRefPubMedPubMedCentral

33.

Logge W, Cheng D, Chesworth R, Bhatia S, Garner B, Kim WS et al (2012) Role of Abca7 in mouse behaviours relevant to neurodegenerative diseases. PLoS One 7:e45959. https://doi.org/10.1371/journal.pone.0045959 CrossRefPubMedPubMedCentral

34.

Harold D, Abraham R, Hollingworth P, Sims R, Gerrish A, Hamshere ML et al (2009) Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat Genet 41:1088–1093. https://doi.org/10.1038/ng.440 CrossRefPubMedPubMedCentral

35.

Hollingworth P, Harold D, Sims R, Gerrish A, Lambert J-C, Carrasquillo MM et al (2011) Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease. Nat Genet 43:429–435. https://doi.org/10.1038/ng.803 CrossRefPubMedPubMedCentral

36.

Lambert J-C, Heath S, Even G, Campion D, Sleegers K, Hiltunen M et al (2009) Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease. Nat Genet 41:1094–1099. https://doi.org/10.1038/ng.439 CrossRefPubMed

37.

Lambert J-C, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R, Bellenguez C et al (2013) Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat Genet 45:1452–1458. https://doi.org/10.1038/ng.2802 CrossRefPubMedPubMedCentral

38.

Naj AC, Jun G, Beecham GW, Wang L, Vardarajan BN, Buros J et al (2011) Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer’s disease. Nat Genet 43:436–441. https://doi.org/10.1038/ng.801 CrossRefPubMedPubMedCentral

39.

Reitz C, Wang L, Lin C, Larson EB, Graff-radford NR, Evans D et al (2013) Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E and the risk of late-onset Alzheimer disease in African Americans. JAMA 309:1483–1492CrossRefPubMedPubMedCentral

40.

Seshadri S, Fitzpatrick AL, Ikram MA, DeStefano AL, Gudnason V, Boada M et al (2010) Genome-wide analysis of genetic loci associated with Alzheimer disease. JAMA 303:1832–1840. https://doi.org/10.1001/jama.2010.574 CrossRefPubMedPubMedCentral

41.

Rentzsch P, Witten D, Cooper GM, Shendure J, Kircher M (2018) CADD: predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res 47:1–9. https://doi.org/10.1093/nar/gky1016 CrossRef

42.

Machiela MJ, Chanock SJ (2015) LDlink: a web-based application for exploring population-specific haplotype structure and linking correlated alleles of possible functional variants. Bioinformatics 31:3555–3557. https://doi.org/10.1093/bioinformatics/btv402 CrossRefPubMedPubMedCentral

43.

Almeida JFF, dos Santos LR, Trancozo M, de Paula F (2018) Updated meta-analysis of BIN1, CR1, MS4A6A, CLU, and ABCA7 variants in Alzheimer’s disease. J Mol Neurosci 64:471–477. https://doi.org/10.1007/s12031-018-1045-y CrossRefPubMed

44.

Shulman JM, Chen K, Keenan BT, Chibnik LB, Fleisher A, Thiyyagura P et al (2013) Genetic susceptibility for Alzheimer disease neuritic plaque pathology. JAMA Neurol 70:1150–1157. https://doi.org/10.1001/jamaneurol.2013.2815 CrossRefPubMedPubMedCentral

45.

Hughes TM, Lopez OL, Evans RW, Kamboh MI, Williamson JD, Klunk WE et al (2014) Markers of cholesterol transport are associated with amyloid deposition in the brain. Neurobiol Aging 35:802–807. https://doi.org/10.1016/j.neurobiolaging.2013.09.040 CrossRefPubMed

46.

Apostolova LG, Risacher SL, Duran T, Stage EC, Goukasian N, West JD et al (2018) Associations of the top 20 Alzheimer disease risk variants with brain amyloidosis. JAMA Neurol 75:328–341. https://doi.org/10.1001/jamaneurol.2017.4198 CrossRefPubMedPubMedCentral

47.

Ma F, Zong Y, Wang H, Li J, Cao X, Tan L (2018) ABCA7 genotype altered Aβ levels in cerebrospinal fluid in Alzheimer’s disease without dementia. Ann Transl Med 6:437. https://doi.org/10.21037/atm.2018.07.04 CrossRefPubMedPubMedCentral

48.

Ramirez LM, Goukasian N, Porat S, Hwang KS, Eastman JA, Hurtz S et al (2016) Common variants in ABCA7 and MS4A6A are associated with cortical and hippocampal atrophy. Neurobiol Aging 39:82–89. https://doi.org/10.1016/j.neurobiolaging.2015.10.037 CrossRefPubMed

49.

Roshchupkin GV, Adams HH, van der Lee SJ, Vernooij MW, van Duijn CM, Uitterlinden AG et al (2016) Fine-mapping the effects of Alzheimer’s disease risk loci on brain morphology. Neurobiol Aging 48:204–211. https://doi.org/10.1016/j.neurobiolaging.2016.08.024 CrossRefPubMed

50.

Stage E, Duran T, Risacher SL, Goukasian N, Do TM, West JD et al (2016) 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 5:53–66. https://doi.org/10.1016/j.dadm.2016.12.003 CrossRef

51.

Sinha N, Reagh ZM, Tustison NJ, Berg CN, Shaw A, Myers CE et al (2018) ABCA7 risk variant in healthy older African Americans is associated with a functionally isolated entorhinal cortex mediating deficient generalization of prior discrimination training. Hippocampus. https://doi.org/10.1002/hipo.23042 CrossRefPubMedPubMedCentral

52.

Wachinger C, Nho K, Saykin AJ, Reuter M, Rieckmann A (2018) A longitudinal imaging genetics study of neuroanatomical asymmetry in Alzheimer’s disease. Biol Psychiatry 84:522–530. https://doi.org/10.1016/j.biopsych.2018.04.017 CrossRefPubMedPubMedCentral

53.

Karch CM, Jeng AT, Nowotny P, Cady J, Cruchaga C, Goate AM (2012) Expression of novel Alzheimer’s disease risk genes in control and Alzheimer’s disease brains. PLoS One 7:e50976. https://doi.org/10.1371/journal.pone.0050976 CrossRefPubMedPubMedCentral

54.

Engelman CD, Koscik RL, Jonaitis EM, Okonkwo OC, Hermann BP, La Rue A et al (2013) Interaction between two cholesterol metabolism genes influences memory: findings from the Wisconsin registry for Alzheimer’s prevention. J Alzheimer’s Dis 36:749–757. https://doi.org/10.3233/JAD-130482 CrossRef

55.

Carrasquillo MM, Khan QUA, Murray ME, Krishnan S, Aakre J, Pankratz VS et al (2014) Late-onset Alzheimer disease genetic variants in posterior cortical atrophy and posterior AD. Neurology 82:1455–1462. https://doi.org/10.1212/WNL.0000000000000335 CrossRefPubMedPubMedCentral

56.

Carrasquillo MM, Crook JE, Pedraza O, Thomas CS, Pankratz VS, Allen M et al (2015) Late-onset Alzheimer’s risk variants in memory decline, incident mild cognitive impairment, and Alzheimer’s disease. Neurobiol Aging 36:60–67. https://doi.org/10.1016/j.neurobiolaging.2014.07.042 CrossRefPubMed

57.

Nettiksimmons J, Tranah G, Evans DS, Yokoyama JS, Yaffe K (2016) Gene-based aggregate SNP associations between candidate AD genes and cognitive decline. Age (Omaha) 38:41. https://doi.org/10.1007/s11357-016-9885-2 CrossRef

58.

Schott JM, Crutch SJ, Carrasquillo MM, Uphill J, Shakespeare TJ, Ryan NS et al (2016) Genetic risk factors for the posterior cortical atrophy variant of Alzheimer’s disease. Alzheimer’s Dement 12:862–871. https://doi.org/10.1016/j.jalz.2016.01.010 CrossRef

59.

Andrews SJ, Das D, Anstey KJ, Easteal S (2017) Late onset Alzheimer’s disease risk variants in cognitive decline: the PATH through life study. J Alzheimers Dis 57:423–436. https://doi.org/10.3233/JAD-160774 CrossRefPubMed

60.

Monsell SE, Mock C, Fardo DW, Bertelsen S, Cairns NJ, Roe CM et al (2017) Genetic comparison of symptomatic and asymptomatic persons with Alzheimer disease neuropathology. Alzheimer Dis Assoc Disord 31:232–238. https://doi.org/10.1097/WAD.0000000000000179 CrossRefPubMedPubMedCentral

61.

Hohman TJ, Koran ME, Thornton-Wells T, Alzheimer’s Neuroimaging Initiative (2013) Epistatic genetic effects among Alzheimer’s candidate genes. PLoS One 8:e80839. https://doi.org/10.1371/journal.pone.0080839 CrossRefPubMedPubMedCentral

62.

Frisoni GB, Fox NC, Jack CR, Scheltens P, Thompson PM (2010) The clinical use of structural MRI in Alzheimer disease. Nat Rev Neurol 6:67–77. https://doi.org/10.1038/nrneurol.2009.215 CrossRefPubMedPubMedCentral

63.

Vivot A, Glymour MM, Tzourio C, Amouyel P, Chêne G, Dufouil C (2015) Association of Alzheimer’s related genotypes with cognitive decline in multiple domains: results from the three-city Dijon study. Mol Psychiatry 20:1173–1178. https://doi.org/10.1038/mp.2015.62 CrossRefPubMed

64.

Ober C, Vercelli D (2011) Gene-environment interactions in human disease: nuisance or opportunity? Trends Genet 27:107–115. https://doi.org/10.1016/j.tig.2010.12.004 CrossRefPubMedPubMedCentral

65.

Crutch SJ, Lehmann M, Schott JM, Rabinovici GD, Rossor MN, Fox NC (2012) Posterior cortical atrophy. Lancet Neurol 11:170–178. https://doi.org/10.1016/S1474-4422(11)70289-7 CrossRefPubMedPubMedCentral

66.

Logue MW, Schu M, Vardarajan BN, Farrell J, Lunetta KL, Jun G et al (2014) Search for age-related macular degeneration risk variants in Alzheimer disease genes and pathways. Neurobiol Aging 35:1510.e7–1510.e18. https://doi.org/10.1016/j.neurobiolaging.2013.12.007 CrossRef

67.

Kjeldsen EW, Tybjærg-Hansen A, Nordestgaard BG, Frikke-Schmidt R (2018) ABCA7 and risk of dementia and vascular disease in the Danish population. Ann Clin Transl Neurol 5:41–51. https://doi.org/10.1002/acn3.506 CrossRefPubMed

68.

Vasquez JB, Fardo DW, Estus S (2013) ABCA7 expression is associated with Alzheimer’s disease polymorphism and disease status. Neurosci Lett 556:58–62. https://doi.org/10.1016/j.neulet.2013.09.058 CrossRefPubMed

69.

Allen M, Zou F, Chai HS, Younkin CS, Crook J, Pankratz VS et al (2012) Novel late-onset Alzheimer disease loci variants associate with brain gene expression. Neurology 79:221–228. https://doi.org/10.1212/WNL.0b013e3182605801 CrossRefPubMedPubMedCentral

70.

Bamji-Mirza M, Li Y, Najem D, Liu QY, Walker D, Lue L-F et al (2016) 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 53:875–892. https://doi.org/10.3233/JAD-150965 CrossRef

71.

Cuyvers E, De Roeck A, Van den Bossche T, Van Cauwenberghe C, Bettens K, Vermeulen S et al (2015) Mutations in ABCA7 in a Belgian cohort of Alzheimer’s disease patients: a targeted resequencing study. Lancet Neurol 14:814–822. https://doi.org/10.1016/S1474-4422(15)00133-7 CrossRefPubMed

72.

Kunkle BW, Carney RM, Kohli MA, Naj AC, Hamilton-Nelson KL, Whitehead PL et al (2017) Targeted sequencing of ABCA7 identifies splicing, stop-gain and intronic risk variants for Alzheimer disease. Neurosci Lett 649:124–129. https://doi.org/10.1016/j.neulet.2017.04.014 CrossRefPubMed

73.

De Roeck A, Duchateau L, Van Dongen J, Cacace R, Bjerke M, Van den Bossche T et al (2018) An intronic VNTR affects splicing of ABCA7 and increases risk of Alzheimer’s disease. Acta Neuropathol 135:827–837. https://doi.org/10.1007/s00401-018-1841-z CrossRefPubMedPubMedCentral

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. https://doi.org/10.1101/439026

75.

Cukier HN, Kunkle BW, Vardarajan BN, Rolati S, Hamilton-Nelson KL, Kohli MA et al (2016) ABCA7 frameshift deletion associated with Alzheimer disease in African Americans. Neurol Genet 2:e79. https://doi.org/10.1212/NXG.0000000000000079 CrossRefPubMedPubMedCentral

76.

Logue MW, Lancour D, Farrell J, Simkina I, Fallin MD, Lunetta KL et al (2018) Targeted sequencing of Alzheimer disease genes in African Americans implicates novel risk variants. Front Neurosci 12:1–11. https://doi.org/10.3389/fnins.2018.00592 CrossRef

77.

Steinberg S, Stefansson H, Jonsson T, Johannsdottir H, Ingason A, Helgason H et al (2015) Loss-of-function variants in ABCA7 confer risk of Alzheimer’s disease. Nat Genet 47:445–447. https://doi.org/10.1038/ng.3246 CrossRefPubMed

78.

Chen JA, Wang Q, Davis-Turak J, Li Y, Karydas AM, Hsu SC et al (2015) A multiancestral genome-wide exome array study of Alzheimer Disease, frontotemporal dementia, and progressive supranuclear palsy. JAMA Neurol 72:414–422. https://doi.org/10.1001/jamaneurol.2014.4040 CrossRefPubMedPubMedCentral

79.

Vardarajan BN, Ghani M, Kahn A, Sheikh S, Sato C, Barral S et al (2015) Rare coding mutations identified by sequencing of Alzheimer disease genome-wide association studies loci. Ann Neurol 78:487–498. https://doi.org/10.1002/ana.24466 CrossRefPubMedPubMedCentral

80.

Allen M, Lincoln SJ, Corda M, Watzlawik JO, Carrasquillo MM, Reddy JS et al (2017) ABCA7 loss-of-function variants, expression, and neurologic disease risk. Neurol Genet 3:e126. https://doi.org/10.1212/NXG.0000000000000126 CrossRefPubMedPubMedCentral

81.

Bellenguez C, Charbonnier C, Grenier-Boley B, Quenez O, Le Guennec K, Nicolas G et al (2017) Contribution to Alzheimer’s disease risk of rare variants in TREM2, SORL1, and ABCA7 in 1779 cases and 1273 controls. Neurobiol Aging 59:220.e1–220.e9. https://doi.org/10.1016/j.neurobiolaging.2017.07.001 CrossRef

82.

Del-Aguila JL, Fernández MV, Jimenez J, Black K, Ma S, Deming Y et al (2015) Role of ABCA7 loss-of-function variant in Alzheimer’s disease: a replication study in European-Americans. Alzheimers Res Ther 7:73. https://doi.org/10.1186/s13195-015-0154-x CrossRefPubMedPubMedCentral

83.

Le Guennec K, Nicolas G, Quenez O, Charbonnier C, Wallon D, Bellenguez C et al (2016) ABCA7 rare variants and Alzheimer disease risk. Neurology 86:2134–2137. https://doi.org/10.1212/WNL.0000000000002627 CrossRefPubMedPubMedCentral

84.

Patel T, Brookes KJ, Turton J, Chaudhury S, Guetta-Baranes T, Guerreiro R et al (2018) Whole-exome sequencing of the BDR cohort: evidence to support the role of the PILRA gene in Alzheimer’s disease. Neuropathol Appl Neurobiol 44:506–521. https://doi.org/10.1111/nan.12452 CrossRefPubMedPubMedCentral

85.

De Roeck A, Van den Bossche T, van der Zee J, Verheijen J, De Coster W, Van Dongen J et al (2017) Deleterious ABCA7 mutations and transcript rescue mechanisms in early onset Alzheimer’s disease. Acta Neuropathol 134:475–487. https://doi.org/10.1007/s00401-017-1714-x CrossRefPubMedPubMedCentral

86.

Sassi C, Nalls MA, Ridge PG, Gibbs JR, Ding J, Lupton MK et al (2016) ABCA7 p. G215S as potential protective factor for Alzheimer’s disease. Neurobiol Aging 46:235.e1–235.e9. https://doi.org/10.1016/j.neurobiolaging.2016.04.004 CrossRef

87.

Schwarzer G (2007) meta: an R package for meta-analysis. R News 7:40–45

88.

Gordon M, Lumley T (2017) forestplot: advanced forest plot using “grid” graphics. https://cran.r-project.org/package=forestplot

89.

Vasquez JB, Simpson JF, Harpole R, Estus S (2017) Alzheimer’s disease genetics and ABCA7 splicing. J Alzheimers Dis 59:633–641. https://doi.org/10.3233/JAD-170872 CrossRefPubMedPubMedCentral

90.

Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T et al (2016) Analysis of protein-coding genetic variation in 60,706 humans. Nature 536:285–291. https://doi.org/10.1038/nature19057 CrossRefPubMedPubMedCentral

91.

Strachan T, Read A (2011) Human Molecular Genetics, 4th edn. Garland Science, Taylor and Francis Group LLC, London, p 390CrossRef

92.

Van den Bossche T, Sleegers K, Cuyvers E, Engelborghs S, Sieben A, De Roeck A et al (2016) Phenotypic characteristics of Alzheimer patients carrying an ABCA7 mutation. Neurology 86:2126–2133. https://doi.org/10.1212/WNL.0000000000002628 CrossRefPubMedPubMedCentral

93.

May P, Pichler S, Hartl D, Bobbili DR, Mayhaus M, Spaniol C et al (2018) Rare ABCA7 variants in 2 German families with Alzheimer disease. Neurol Genet 4:e224. https://doi.org/10.1212/NXG.0000000000000224 CrossRefPubMedPubMedCentral

94.

Nuytemans K, Maldonado L, Ali A, John-Williams K, Beecham GW, Martin E et al (2016) Overlap between Parkinson disease and Alzheimer disease in ABCA7 functional variants. Neurol Genet 2:e44. https://doi.org/10.1212/NXG.0000000000000044 CrossRefPubMedPubMedCentral

95.

Martiskainen H, Herukka SK, Stančáková A, Paananen J, Soininen H, Kuusisto J et al (2017) Decreased plasma β-amyloid in the Alzheimer’s disease APP A673T variant carriers. Ann Neurol 82:128–132. https://doi.org/10.1002/ana.24969 CrossRefPubMed

96.

Hansson O, Zetterberg H, Vanmechelen E, Vanderstichele H, Andreasson U, Londos E et al (2010) Evaluation of plasma Aβ40and Aβ42as predictors of conversion to Alzheimer’s disease in patients with mild cognitive impairment. Neurobiol Aging 31:357–367. https://doi.org/10.1016/j.neurobiolaging.2008.03.027 CrossRefPubMed

97.

Lee S, Emond MJ, Bamshad MJ, Barnes KC, Rieder MJ, Nickerson DA et al (2012) Optimal unified approach for rare-variant association testing with application to small-sample case-control whole-exome sequencing studies. Am J Hum Genet 91:224–237. https://doi.org/10.1016/j.ajhg.2012.06.007 CrossRefPubMedPubMedCentral

98.

Jones PA (2012) Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 13:484–492. https://doi.org/10.1038/nrg3230 CrossRefPubMed

99.

De Jager PL, Srivastava G, Lunnon K, Burgess J, Schalkwyk LC, Yu L et al (2014) Alzheimer’s disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci. Nat Neurosci 17:1156–1163. https://doi.org/10.1038/nn.3786 CrossRefPubMedPubMedCentral

100.

Yu L, Chibnik LB, Srivastava GP, Pochet N, Yang J, Xu J et al (2015) Association of brain DNA methylation in SORL1, ABCA7, HLA-DRB5, SLC24A4, and BIN1 With pathological diagnosis of Alzheimer disease. JAMA Neurol 72(1):15–24. https://doi.org/10.1001/jamaneurol.2014.3049 CrossRefPubMedPubMedCentral

101.

Chibnik LB, Yu L, Eaton ML, Srivastava G, Schneider JA, Kellis M et al (2015) Alzheimer’s loci: epigenetic associations and interaction with genetic factors. Ann Clin Transl Neurol 2:636–647. https://doi.org/10.1002/acn3.201 CrossRefPubMedPubMedCentral

102.

Reddington JP, Perricone SM, Nestor CE, Reichmann J, Youngson NA, Suzuki M et al (2013) Redistribution of H3K27me3 upon DNA hypomethylation results in de-repression of Polycomb target genes. Genome Biol 15:45. https://doi.org/10.1186/gb-2013-14-3-r25 CrossRef

103.

Humphries C, Kohli MA, Whitehead P, Mash DC, Pericak-Vance MA, Gilbert J (2015) Alzheimer disease (AD) specific transcription, DNA methylation and splicing in twenty AD associated loci. Mol Cell Neurosci 67:37–45. https://doi.org/10.1016/j.mcn.2015.05.003 CrossRefPubMedPubMedCentral

104.

Lunnon K, Smith R, Hannon E, De Jager PL, Srivastava G, Volta M et al (2014) Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer’s disease. Nat Neurosci 17:1164–1170. https://doi.org/10.1038/nn.3782 CrossRefPubMedPubMedCentral

105.

Yamazaki K, Yoshino Y, Mori T, Yoshida T, Ozaki Y, Sao T et al (2017) Gene expression and methylation analysis of ABCA7 in patients with Alzheimer’s disease. J Alzheimers Dis 57:171–181. https://doi.org/10.3233/JAD-161195 CrossRefPubMed

106.

Ikeda Y, Abe-Dohmae S, Munehira Y, Aoki R, Kawamoto S, Furuya A et al (2003) Posttranscriptional regulation of human ABCA7 and its function for the apoA-I-dependent lipid release. Biochem Biophys Res Commun 311:313–318. https://doi.org/10.1016/j.bbrc.2003.10.002 CrossRefPubMed

107.

Frankish A, Diekhans M, Ferreira A-M, Johnson R, Jungreis I, Loveland J et al (2018) GENCODE reference annotation for the human and mouse genomes. Nucleic Acids Res 47:766–773. https://doi.org/10.1093/nar/gky955 CrossRef

108.

Raj T, Li YI, Wong G, Humphrey J, Wang M, Ramdhani S et al (2018) Integrative transcriptome analyses of the aging brain implicate altered splicing in Alzheimer’s disease susceptibility. Nat Genet 50:1584–1592. https://doi.org/10.1038/s41588-018-0238-1 CrossRefPubMedPubMedCentral

109.

Li YI, Knowles DA, Humphrey J, Barbeira AN, Dickinson SP, Im HK et al (2018) Annotation-free quantification of RNA splicing using LeafCutter. Nat Genet 50:151–158. https://doi.org/10.1038/s41588-017-0004-9 CrossRefPubMed

110.

Elsnerova K, Bartakova A, Tihlarik J, Bouda J, Rob L, Skapa P et al (2017) Gene expression profiling reveals novel candidate markers of ovarian carcinoma intraperitoneal metastasis. J Cancer 8:3598–3606. https://doi.org/10.7150/jca.20766 CrossRefPubMedPubMedCentral

111.

Liu X, Li Q, Zhou J, Zhang S (2018) 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 16:5868–5874. https://doi.org/10.3892/ol.2018.9366 CrossRefPubMedPubMedCentral

112.

Mohelnikova-Duchonova B, Brynychova V, Oliverius M, Honsova E, Kala Z, Muckova K et al (2013) Differences in transcript levels of ABC transporters between pancreatic adenocarcinoma and nonneoplastic tissues. Pancreas 42:707–716. https://doi.org/10.1097/MPA.0b013e318279b861 CrossRefPubMed

113.

Heimerl S, Bosserhoff AK, Langmann T, Ecker J, Schmitz G (2007) Mapping ATP-binding cassette transporter gene expression profiles in melanocytes and melanoma cells. Melanoma Res 17:265–273. https://doi.org/10.1097/CMR.0b013e3282a7e0b9 CrossRefPubMed

114.

Tabarés-Seisdedos R, Rubenstein JL (2013) Inverse cancer comorbidity: a serendipitous opportunity to gain insight into CNS disorders. Nat Rev Neurosci 14:293–304. https://doi.org/10.1038/nrn3464 CrossRefPubMed

115.

Ibáñez K, Boullosa C, Tabarés-Seisdedos R, Baudot A, Valencia A (2014) Molecular evidence for the inverse comorbidity between central nervous system disorders and cancers detected by transcriptomic meta-analyses. PLoS Genet 10:1–7. https://doi.org/10.1371/journal.pgen.1004173 CrossRef

116.

Feng YCA, Cho K, Lindström S, Kraft P, Cormack J, Blalock K et al (2017) Investigating the genetic relationship between Alzheimer’s disease and cancer using GWAS summary statistics. Hum Genet 136:1341–1351. https://doi.org/10.1007/s00439-017-1831-6 CrossRefPubMedPubMedCentral

117.

Witte JS, Visscher PM, Wray NR (2014) The contribution of genetic variants to disease depends on the ruler. Nat Publ Gr 15:765–776. https://doi.org/10.1038/nrg3786 CrossRef

118.

Patel H, Dobson RJB, Newhouse SJ (2019) Meta-analysis of Alzheimer’s disease brain transcriptomic data. bioRxiv. https://doi.org/10.1101/480459

119.

Grindberg RV, Yee-Greenbaum JL, McConnell MJ, Novotny M, O’Shaughnessy AL, Lambert GM et al (2013) RNA-sequencing from single nuclei. Proc Natl Acad Sci 110:19802–19807. https://doi.org/10.1073/pnas.1319700110 CrossRefPubMedPubMedCentral

120.

Lein E, Borm LE, Linnarsson S (2017) The promise of spatial transcriptomics for neuroscience in the era of molecular cell typing. Science 358:64–69. https://doi.org/10.1126/science.aan6827 CrossRefPubMed

121.

Garalde DR, Snell EA, Jachimowicz D, Sipos B, Lloyd JH, Bruce M et al (2018) Highly parallel direct RNA sequencing on an array of nanopores. Nat Methods 15:201–206. https://doi.org/10.1038/nmeth.4577 CrossRefPubMed

122.

Rhoads A, Au KF (2015) PacBio sequencing and its applications. Genom, Proteom Bioinforma 13:278–289. https://doi.org/10.1016/j.gpb.2015.08.002 CrossRef

123.

Jones VC, Atkinson-Dell R, Verkhratsky A, Mohamet L (2017) Aberrant iPSC-derived human astrocytes in Alzheimer’s disease. Cell Death Dis 8:1–11. https://doi.org/10.1038/cddis.2017.89 CrossRef

124.

Kelava I, Lancaster MA (2016) Dishing out mini-brains: current progress and future prospects in brain organoid research. Dev Biol 420:199–209. https://doi.org/10.1016/j.ydbio.2016.06.037 CrossRefPubMedPubMedCentral

125.

Qian H, Zhao X, Cao P, Lei J, Yan N, Gong X (2017) Structure of the human lipid exporter ABCA1. Cell. https://doi.org/10.1016/j.cell.2017.05.020 CrossRefPubMedPubMedCentral

126.

Watson M, Warr A (2019) Errors in long-read assemblies can critically affect protein prediction. Nat Biotechnol 15:1–3. https://doi.org/10.1038/s41587-018-0004-z CrossRef

Title: The role of ABCA7 in Alzheimer’s disease: evidence from genomics, transcriptomics and methylomics
Authors: Arne De Roeck
Christine Van Broeckhoven
Kristel Sleegers
Publication date: 01-08-2019
Publisher: Springer Berlin Heidelberg
Keywords: Alzheimer's Disease
Alzheimer's Disease
Published in: Acta Neuropathologica / Issue 2/2019
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-019-01994-1

At a glance: The ONWARDS insulin icodec trials

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

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

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