The ABCA7 transporter, brain lipids and Alzheimer’s disease

References

• Chan RB, Oliveira TG, Cortes EP et al. Comparative lipidomic analysis of mouse and human brain with Alzheimer disease. J. Biol. Chem. 287(4), 2678–2688 (2012). ▪ Provides a comprehensive analysis of lipid changes in Alzheimer’s disease (AD).
   Google Scholar
• Di Paolo G, Kim TW. Linking lipids to Alzheimer’s disease: cholesterol and beyond.Nat. Rev. Neurosci. 12(5), 284–296 (2011). ▪ Provides a comprehensive analysis of lipid changes in AD.
   Google Scholar
• Alzheimer A, Stelzmann RA, Schnitzlein HN, Murtagh FR. An English translation of Alzheimer’s 1907 paper, “Uber eine eigenartige Erkankung der Hirnrinde”. Clin. Anat. 8(6), 429–431 (1995).
   Google Scholar
• Tanzi RE, Bertram L. Twenty years of the Alzheimer’s disease amyloid hypothesis: a genetic perspective. Cell 120(4), 545–555 (2005).
   Google Scholar
• Glenner GG, Wong CW. Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun. 120(3), 885–890 (1984).
   Google Scholar
• Goldgaber D, Lerman MI, Mcbride OW, Saffiotti U, Gajdusek DC. Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer’s disease.Science 235(4791), 877–880 (1987).
   Google Scholar
• Kang J, Lemaire HG, Unterbeck A et al. The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor.Nature 325(6106), 733–736 (1987).
   Google Scholar
• Robakis NK, Ramakrishna N, Wolfe G, Wisniewski HM. Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides. Proc. Natl Acad. Sci. USA 84(12), 4190–4194 (1987).
   Google Scholar
• Tanzi RE, Gusella JF, Watkins PC et al. Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Science 235(4791), 880–884 (1987).
   Google Scholar
• Schellenberg GD, Bird TD, Wijsman EM et al. Genetic linkage evidence for a familial Alzheimer’s disease locus on chromosome 14.Science 258(5082), 668–671 (1992).
   Google Scholar
• Sherrington R, Rogaev EI, Liang Y et al. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer’s disease.Nature 375(6534), 754–760 (1995).
   Google Scholar
• Levy-Lahad E, Wasco W, Poorkaj P et al. Candidate gene for the chromosome 1 familial Alzheimer’s disease locus. Science 269(5226), 973–977 (1995).
   Google Scholar
• Rogaev EI, Sherrington R, Rogaeva EA et al. Familial Alzheimer’s disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer’s disease type 3 gene. Nature 376(6543), 775–778 (1995).
   Google Scholar
• Pericak-Vance MA, Bebout JL, Gaskell PC, JR et al. Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage.Am. J. Hum. Genet. 48(6), 1034–1050 (1991).
   Google Scholar
• Strittmatter WJ, Saunders AM, Schmechel D et al. Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc. Natl Acad. Sci. USA 90(5), 1977–1981 (1993).
   Google Scholar
• Schmechel DE, Saunders AM, Strittmatter WJ et al. Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. Proc. Natl Acad. Sci. USA 90(20), 9649–9653 (1993).
   Google Scholar
• Haass C, Selkoe DJ. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide. Nat. Rev. Mol. Cell Biol. 8(2), 101–112 (2007).
   Google Scholar
• Mclean CA, Cherny RA, Fraser FW et al. Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer’s disease. Ann. Neurol. 46(6), 860–866 (1999).
   Google Scholar
• Kuo YM, Webster S, Emmerling MR, De Lima N, Roher AE. Irreversible dimerization/tetramerization and posttranslational modifications inhibit proteolytic degradation of A beta peptides of Alzheimer’s disease. Biochim. Biophys. Acta 1406(3), 291–298 (1998).
   Google Scholar
• Li S, Hong S, Shepardson NE, Walsh DM, Shankar GM, Selkoe D. Soluble oligomers of amyloid beta protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake. Neuron 62(6), 788–801 (2009).
   Google Scholar
• Cheng IH, Scearce-Levie K, Legleiter J et al. Accelerating amyloid-beta fibrillization reduces oligomer levels and functional deficits in Alzheimer disease mouse models. J. Biol. Chem. 282(33), 23818–23828 (2007).
   Google Scholar
• Hollingworth P, Harold D, Sims R et al. Common variants at ABCA7, MS4A6A/ MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease. Nat. Genet. 43(5), 429–435 (2011). ▪▪ Describes how a genome-wide association study identified ABCA7 as a susceptibility factor for AD.
   Google Scholar
• Eisenstein M. Genetics: finding risk factors. Nature 475(7355), S20–S22 (2011).
   Google Scholar
• Small SA, Gandy S. Sorting through the cell biology of Alzheimer’s disease: intracellular pathways to pathogenesis. Neuron 52(1), 15–31 (2006).
   Google Scholar
• Grosgen S, Grimm MO, Friess P, Hartmann T. Role of amyloid beta in lipid homeostasis. Biochim. Biophys. Acta 1801(8), 966–974 (2010).
   Google Scholar
• Simons M, Keller P, De Strooper B, Beyreuther K, Dotti CG, Simons K. Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons. Proc. Natl Acad. Sci. USA 95(11), 6460–6464 (1998).
   Google Scholar
• Vetrivel KS, Thinakaran G. Membrane rafts in Alzheimer’s disease beta-amyloid production. Biochim. Biophys. Acta 1801(8), 860–867 (2010).
   Google Scholar
• Ehehalt R, Keller P, Haass C, Thiele C, Simons K. Amyloidogenic processing of the Alzheimer beta-amyloid precursor protein depends on lipid rafts. J. Cell Biol. 160(1), 113–123 (2003).
   Google Scholar
• Vetrivel KS, Meckler X, Chen Y et al. Alzheimer disease Abeta production in the absence of S-palmitoylation-dependent targeting of BACE1 to lipid rafts. J. Biol. Chem. 284(6), 3793–3803 (2009).
   Google Scholar
• Hattori C, Asai M, Onishi H et al. BACE1 interacts with lipid raft proteins. J. Neurosci. Res. 84(4), 912–917 (2006).
   Google Scholar
• Urano Y, Hayashi I, Isoo N et al. Association of active gamma-secretase complex with lipid rafts. J. Lipid Res. 46(5), 904–912 (2005).
   Google Scholar
• Marquer C, Devauges V, Cossec JC et al. Local cholesterol increase triggers amyloid precursor protein-Bace1 clustering in lipid rafts and rapid endocytosis. FASEB J. 25(4), 1295–1305 (2011).
   Google Scholar
• Schneider A, Rajendran L, Honsho M et al. Flotillin-dependent clustering of the amyloid precursor protein regulates its endocytosis and amyloidogenic processing in neurons. J. Neurosci. 28(11), 2874–2882 (2008).
   Google Scholar
• Martin V, Fabelo N, Santpere G et al. Lipid alterations in lipid rafts from Alzheimer’s disease human brain cortex. J. Alzheimers Dis. 19(2), 489–502 (2010).
   Google Scholar
• Kokjohn TA, Van Vickle GD, Maarouf CL et al. Chemical characterization of proinflammatory amyloid-beta peptides in human atherosclerotic lesions and platelets. Biochim. Biophys. Acta 1812(11), 1508–1514 (2011).
   Google Scholar
• Hannun YA, Obeid LM. Principles of bioactive lipid signalling: lessons from sphingolipids. Nat. Rev. Mol. Cell Biol. 9(2), 139–150 (2008).
   Google Scholar
• Posse De Chaves E, Sipione S. Sphingolipids and gangliosides of the nervous system in membrane function and dysfunction. FEBS Lett. 584(9), 1748–1759 (2010).
   Google Scholar
• He X, Huang Y, Li B, Gong CX, Schuchman EH. Deregulation of sphingolipid metabolism in Alzheimer’s disease. Neurobiol. Aging 31(3), 398–408 (2010).
   Google Scholar
• Haughey NJ, Bandaru VV, Bae M, Mattson MP. Roles for dysfunctional sphingolipid metabolism in Alzheimer’s disease neuropathogenesis. Biochim. Biophys. Acta 1801(8), 878–886 (2010).
   Google Scholar
• Puglielli L, Ellis BC, Saunders AJ, Kovacs DM. Ceramide stabilizes beta-site amyloid precursor protein-cleaving enzyme 1 and promotes amyloid beta-peptide biogenesis. J. Biol. Chem. 278(22), 19777–19783 (2003).
   Google Scholar
• Grimm MO, Grimm HS, Patzold AJ et al. Regulation of cholesterol and sphingomyelin metabolism by amyloid-beta and presenilin.Nat. Cell Biol. 7(11), 1118–1123 (2005).
   Google Scholar
• Hooff GP, Wood WG, Muller WE, Eckert GP. Isoprenoids, small GTPases and Alzheimer’s disease. Biochim. Biophys. Acta 1801(8), 896–905 (2010).
   Google Scholar
• Cole SL, Vassar R. Isoprenoids and Alzheimer’s disease: a complex relationship.Neurobiol. Dis. 22(2), 209–222 (2006).
   Google Scholar
• Oliveira TG, Di Paolo G. Phospholipase D in brain function and Alzheimer’s disease.Biochim. Biophys. Acta 1801(8), 799–805 (2010).
   Google Scholar
• Sanchez-Mejia RO, Newman JW, Toh S et al. Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer’s disease. Nat. Neurosci. 11(11), 1311–1318 (2008).
   Google Scholar
• Ariga T, McDonald MP, Yu RK. Role of ganglioside metabolism in the pathogenesis of Alzheimer’s disease – a review. J. Lipid Res. 49(6), 1157–1175 (2008).
   Google Scholar
• Matsuzaki K, Kato K, Yanagisawa K. Abeta polymerization through interaction with membrane gangliosides. Biochim. Biophys. Acta 1801(8), 868–877 (2010).
   Google Scholar
• Kracun I, Rosner H, Drnovsek V, Heffer-Lauc M, Cosovic C, Lauc G. Human brain gangliosides in development, aging and disease. Int. J. Dev. Biol. 35(3), 289–295 (1991).
   Google Scholar
• Han X, Holtzman DM, McKeel DW Jr. Plasmalogen deficiency in early Alzheimer’s disease subjects and in animal models: molecular characterization using electrospray ionization mass spectrometry. J. Neurochem. 77(4), 1168–1180 (2001). ▪ Finds decreased plasmalogens in early AD subjects and AD mouse models, providing further evidence of altered lipid homeostasis.
   Google Scholar
• Di Paolo G, De Camilli P. Phosphoinositides in cell regulation and membrane dynamics.Nature 443(7112), 651–657 (2006).
   Google Scholar
• Stokes CE, Hawthorne JN. Reduced phosphoinositide concentrations in anterior temporal cortex of Alzheimer-diseased brains. J. Neurochem. 48(4), 1018–1021 (1987).
   Google Scholar
• Landman N, Jeong SY, Shin SY et al. Presenilin mutations linked to familial Alzheimer’s disease cause an imbalance in phosphatidylinositol 4,5-bisphosphate metabolism. Proc. Natl Acad. Sci. USA 103(51), 19524–19529 (2006).
   Google Scholar
• Berman DE, Dall’Armi C, Voronov SV et al. Oligomeric amyloid-beta peptide disrupts phosphatidylinositol-4,5-bisphosphate metabolism. Nat. Neurosci. 11(5), 547–554 (2008).
   Google Scholar
• Shui G, Guan XL, Low CP et al. Toward one step analysis of cellular lipidomes using liquid chromatography coupled with mass spectrometry: application to Saccharomyces cerevisiae and Schizosaccharomyces pombe lipidomics. Mol. Biosyst. 6(6), 1008–1017 (2010).
   Google Scholar
• Foley P. Lipids in Alzheimer’s disease: a century-old story. Biochim. Biophys. Acta 1801(8), 750–753 (2010).
   Google Scholar
• Hartmann T, Kuchenbecker J, Grimm MO. Alzheimer’s disease: the lipid connection. J. Neurochem. 103(Suppl. 1), 159–170 (2007).
   Google Scholar
• Dietschy JM, Turley SD. Cholesterol metabolism in the brain. Curr. Opin. Lipidol. 12(2), 105–112 (2001).
   Google Scholar
• Vance JE, Hayashi H, Karten B. Cholesterol homeostasis in neurons and glial cells. Semin. Cell Dev. Biol. 16(2), 193–212 (2005).
   Google Scholar
• Chang TY, Chang CC, Ohgami N, Yamauchi Y. Cholesterol sensing, trafficking, and esterification. Annu. Rev. Cell Dev. Biol. 22, 129–157 (2006).
   Google Scholar
• Hirsch-Reinshagen V, Burgess BL, Wellington CL. Why lipids are important for Alzheimer disease? Mol. Cell. Biochem. 326(1–2), 121–129 (2009).
   Google Scholar
• Civeira F, Pocovi M, Cenarro A et al. Apo E variants in patients with type III hyperlipoproteinemia. Atherosclerosis 127(2), 273–282 (1996).
   Google Scholar
• Breslow JL, Zannis VI, Sangiacomo TR, Third JL, Tracy T, Glueck CJ. Studies of familial type III hyperlipoproteinemia using as a genetic marker the apoE phenotype E2/2.J. Lipid Res. 23(8), 1224–1235 (1982).
   Google Scholar
• Feussner G, Feussner V, Hoffmann MM, Lohrmann J, Wieland H, Marz W. Molecular basis of type III hyperlipoproteinemia in Germany. Hum. Mutat. 11(6), 417–423 (1998).
   Google Scholar
• Jiang Q, Lee CY, Mandrekar S et al. ApoE promotes the proteolytic degradation of Abeta. Neuron 58(5), 681–693 (2008).
   Google Scholar
• Boyles JK, Pitas RE, Wilson E, Mahley RW, Taylor JM. Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system. J. Clin. Invest. 76(4), 1501–1513 (1985).
   Google Scholar
• Pitas RE, Boyles JK, Lee SH, Hui D, Weisgraber KH. Lipoproteins and their receptors in the central nervous system. Characterization of the lipoproteins in cerebrospinal fluid and identification of apolipoprotein B,E(LDL) receptors in the brain. J. Biol. Chem. 262(29), 14352–14360 (1987).
   Google Scholar
• Verghese PB, Castellano JM, Holtzman DM. Apolipoprotein E in Alzheimer’s disease and other neurological disorders. Lancet Neurol. 10(3), 241–252 (2011). ▪ Review of the role of ApoE in AD pathogenesis.
   Google Scholar
• Kim J, Basak JM, Holtzman DM. The role of apolipoprotein E in Alzheimer’s disease.Neuron 63(3), 287–303 (2009). ▪ Reviews the role of ApoE in AD pathogenesis.
   Google Scholar
• Corder EH, Saunders AM, Strittmatter WJ et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261(5123), 921–923 (1993).
   Google Scholar
• Saunders AM, Strittmatter WJ, Schmechel D et al. Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer’s disease. Neurology 43(8), 1467–1472 (1993).
   Google Scholar
• Roses AD. Apolipoprotein E alleles as risk factors in Alzheimer’s disease. Annu. Rev. Med. 47, 387–400 (1996).
   Google Scholar
• Poirier J, Davignon J, Bouthillier D, Kogan S, Bertrand P, Gauthier S. Apolipoprotein E polymorphism and Alzheimer’s disease. Lancet 342(8873), 697–699 (1993).
   Google Scholar
• West HL, Rebeck GW, Hyman BT. Frequency of the apolipoprotein E epsilon 2 allele is diminished in sporadic Alzheimer disease. Neurosci. Lett. 175(1–2), 46–48 (1994).
   Google Scholar
• Chiang GC, Insel PS, Tosun D et al. Hippocampal atrophy rates and CSF biomarkers in elderly APOE2 normal subjects.Neurology 75(22), 1976–1981 (2010).
   Google Scholar
• Bandaru VV, Troncoso J, Wheeler D et al. ApoE4 disrupts sterol and sphingolipid metabolism in Alzheimer’s but not normal brain. Neurobiol. Aging 30(4), 591–599 (2009).
   Google Scholar
• Bales KR, Verina T, Cummins DJ et al. Apolipoprotein E is essential for amyloid deposition in the APP(V717F) transgenic mouse model of Alzheimer’s disease. Proc. Natl Acad. Sci. USA 96(26), 15233–15238 (1999).
   Google Scholar
• Holtzman DM, Bales KR, Wu S et al. Expression of human apolipoprotein E reduces amyloid-beta deposition in a mouse model of Alzheimer’s disease. J. Clin. Invest. 103(6), R15–R21 (1999).
   Google Scholar
• Filippini N, Macintosh BJ, Hough MG et al. Distinct patterns of brain activity in young carriers of the APOE-epsilon4 allele. Proc. Natl Acad. Sci. USA 106(17), 7209–7214 (2009).
   Google Scholar
• Reiman EM, Chen K, Liu X et al. Fibrillar amyloid-beta burden in cognitively normal people at 3 levels of genetic risk for Alzheimer’s disease. Proc. Natl Acad. Sci. USA 106(16), 6820–6825 (2009).
   Google Scholar
• Hashimoto T, Serrano-Pozo A, Hori Y et al. Apolipoprotein E, especially apolipoprotein e4, increases the oligomerization of amyloid beta peptide. J. Neurosci. 32(43), 15181–15192 (2012).
   Google Scholar
• Castellano JM, Kim J, Stewart FR et al. Human apoE isoforms differentially regulate brain amyloid-beta peptide clearance. Sci. Transl. Med. 3(89), 89ra57 (2011).
   Google Scholar
• Deane R, Sagare A, Hamm K et al. apoE isoform-specific disruption of amyloid beta peptide clearance from mouse brain. J. Clin. Invest. 118(12), 4002–4013 (2008).
   Google Scholar
• Huang Y. Abeta-independent roles of apolipoprotein E4 in the pathogenesis of Alzheimer’s disease. Trends Mol. Med. 16(6), 287–294 (2010).
   Google Scholar
• Reiman EM, Chen K, Langbaum JB et al. Higher serum total cholesterol levels in late middle age are associated with glucose hypometabolism in brain regions affected by Alzheimer’s disease and normal aging.Neuroimage 49(1), 169–176 (2010).
   Google Scholar
• Caselli RJ, Dueck AC, Osborne D et al. Longitudinal modeling of age-related memory decline and the APOE epsilon4 effect. N. Engl. J. Med. 361(3), 255–263 (2009).
   Google Scholar
• Miyata M, Smith JD. Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and beta-amyloid peptides. Nat. Genet. 14(1), 55–61 (1996).
   Google Scholar
• Harold D, Abraham R, Hollingworth P et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat. Genet. 41(10), 1088–1093 (2009).
   Google Scholar
• Lambert JC, Heath S, Even G et al. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease. Nat. Genet. 41(10), 1094–1099 (2009).
   Google Scholar
• May PC, Johnson SA, Poirier J, Lampert-Etchells M, Finch CE. Altered gene expression in Alzheimer’s disease brain tissue.Can. J. Neurol. Sci. 16(Suppl. 4), 473–476 (1989).
   Google Scholar
• Trougakos IP, Gonos ES. Regulation of clusterin/apolipoprotein J, a functional homologue to the small heat shock proteins, by oxidative stress in ageing and age-related diseases. Free Radic. Res. 40(12), 1324–1334 (2006).
   Google Scholar
• Wilson MR, Easterbrook-Smith SB. Clusterin is a secreted mammalian chaperone. Trends Biochem. Sci. 25(3), 95–98 (2000).
   Google Scholar
• Poon S, Easterbrook-Smith SB, Rybchyn MS, Carver JA, Wilson MR. Clusterin is an ATPindependent chaperone with very broad substrate specificity that stabilizes stressed proteins in a folding-competent state.Biochemistry 39(51), 15953–15960 (2000).
   Google Scholar
• Kumita JR, Poon S, Caddy GL et al. The extracellular chaperone clusterin potently inhibits human lysozyme amyloid formation by interacting with prefibrillar species. J. Mol. Biol. 369(1), 157–167 (2007).
   Google Scholar
• Yerbury JJ, Poon S, Meehan S et al. The extracellular chaperone clusterin influences amyloid formation and toxicity by interacting with prefibrillar structures. FASEB J. 21(10), 2312–2322 (2007).
   Google Scholar
• Shibata M, Yamada S, Kumar SR et al. Clearance of Alzheimer’s amyloid-ss(1–40) peptide from brain by LDL receptor-related protein-1 at the blood–brain barrier. J. Clin. Invest. 106(12), 1489–1499 (2000).
   Google Scholar
• Bell RD, Sagare AP, Friedman AE et al. Transport pathways for clearance of human Alzheimer’s amyloid beta-peptide and apolipoproteins E and J in the mouse central nervous system. J. Cereb. Blood Flow Metab. 27(5), 909–918 (2007).
   Google Scholar
• Demattos RB, Cirrito JR, Parsadanian M et al. ApoE and clusterin cooperatively suppress Abeta levels and deposition: evidence that ApoE regulates extracellular Abeta metabolism in vivo. Neuron 41(2), 193–202 (2004).
   Google Scholar
• De Silva HV, Harmony JA, Stuart WD, Gil CM, Robbins J. Apolipoprotein J: structure and tissue distribution. Biochemistry 29(22), 5380–5389 (1990).
   Google Scholar
• Jenne DE, Tschopp J. Clusterin: the intriguing guises of a widely expressed glycoprotein. Trends Biochem. Sci. 17(4), 154–159 (1992).
   Google Scholar
• De Silva HV, Stuart WD, Duvic CR et al. A 70-kDa apolipoprotein designated ApoJ is a marker for subclasses of human plasma high density lipoproteins. J. Biol. Chem. 265(22), 13240–13247 (1990).
   Google Scholar
• Mccarthy MI, Abecasis GR, Cardon LR et al. Genome-wide association studies for complex traits: consensus, uncertainty and challenges.Nat. Rev. Genet. 9(5), 356–369 (2008).
   Google Scholar
• Moskvina V, Schmidt KM. On multipletesting correction in genome-wide association studies. Genet. Epidemiol. 32(6), 567–573 (2008).
   Google Scholar
• Dudbridge F, Gusnanto A. Estimation of significance thresholds for genomewide association scans. Genet. Epidemiol. 32(3), 227–234 (2008).
   Google Scholar
• Pe’er I, Yelensky R, Altshuler D, Daly MJ. Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Genet. Epidemiol. 32(4), 381–385 (2008).
   Google Scholar
• Bertram L, Tanzi RE. Thirty years of Alzheimer’s disease genetics: the implications of systematic meta-analyses. Nat. Rev. Neurosci. 9(10), 768–778 (2008).
   Google Scholar
• Morgan K. The three new pathways leading to Alzheimer’s disease. Neuropathol. Appl. Neurobiol. 37(4), 353–357 (2011).
   Google Scholar
• Bertram L, Mcqueen MB, Mullin K, Blacker D, Tanzi RE. Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database.Nat. Genet. 39(1), 17–23 (2007).
   Google Scholar
• Kaminski WE, Orso 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. 273(2), 532–538 (2000).
   Google Scholar
• Fitzgerald ML, Mendez AJ, Moore KJ, Andersson LP, Panjeton HA, Freeman MW. ATP-binding cassette transporter A1 contains an NH2-terminal signal anchor sequence that translocates the protein’s first hydrophilic domain to the exoplasmic space. J. Biol. Chem. 276(18), 15137–15145 (2001).
   Google Scholar
• Wang N, Silver DL, Costet P, Tall AR. Specific binding of ApoA-I, enhanced cholesterol efflux, and altered plasma membrane morphology in cells expressing ABC1. J. Biol. Chem. 275(42), 33053–33058 (2000).
   Google Scholar
• Bungert S, Molday LL, Molday RS. Membrane topology of the ATP binding cassette transporter ABCR and its relationship to ABC1 and related ABCA transporters: identification of N-linked glycosylation sites.J. Biol. Chem. 276(26), 23539–23546 (2001).
   Google Scholar
• Beharry S, Zhong M, Molday RS. N-retinylidene-phosphatidylethanolamine is the preferred retinoid substrate for the photoreceptor-specific ABC transporter ABCA4 (ABCR). J. Biol. Chem. 279(52), 53972–53979 (2004).
   Google Scholar
• Yanagi T, Akiyama M, Nishihara H et al. Self-improvement of keratinocyte differentiation defects during skin maturation in ABCA12-deficient harlequin ichthyosis model mice. Am. J. Pathol. 177(1), 106–118 (2010).
   Google Scholar
• Kim WS, Fitzgerald ML, Kang K et al. ABCA7 null mice retain normal macrophage phosphatidylcholine and cholesterol efflux activity despite alterations in adipose mass and serum cholesterol levels. J. Biol. Chem. 280(5), 3989–3995 (2005). ▪▪ Describes the development of the ABCA7-knockout mouse, which will be a useful tool in deciphering the link between the transporter and AD.
   Google Scholar
• Wang N, Lan D, Gerbod-Giannone M et al. ATP-binding cassette transporter A7 (ABCA7) binds apolipoprotein A-I and mediates cellular phospholipid but not cholesterol efflux. J. Biol. Chem. 278(44), 42906–42912 (2003).
   Google Scholar
• Linsel-Nitschke P, Jehle AW, Shan J et al. Potential role of ABCA7 in cellular lipid efflux to apoA-I. J. Lipid Res. 46(1), 86–92 (2005).
   Google Scholar
• Abe-Dohmae S, Ikeda Y, Matsuo M et al. Human ABCA7 supports apolipoproteinmediated release of cellular cholesterol and phospholipid to generate high density lipoprotein. J. Biol. Chem. 279(1), 604–611 (2004).
   Google Scholar
• Jehle AW, Gardai SJ, Li S et al. ATP-binding cassette transporter A7 enhances phagocytosis of apoptotic cells and associated ERK signaling in macrophages. J. Cell Biol. 174(4), 547–556 (2006).
   Google Scholar
• 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. 51(9), 2591–2599 (2010).
   Google Scholar
• 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. 47(9), 1915–1927 (2006).
   Google Scholar
• 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. 18(4), 274–281 (2011).
   Google Scholar
• Cotman CW, Anderson AJ. A potential role for apoptosis in neurodegeneration and Alzheimer’s disease. Mol. Neurobiol. 10(1), 19–45 (1995).
   Google Scholar
• Chan SL, Kim WS, Kwok JB et al. ATP-binding cassette transporter A7 regulates processing of amyloid precursor protein in vitro. J. Neurochem. 106(2), 793–804 (2008). ▪▪ Provides a link between ABCA7 and amyloid-b generation in vitro.
   Google Scholar
• Logge W, Cheng D, Chesworth R et al. Role of Abca7 in mouse behaviours relevant to neurodegenerative diseases. PLoS one 7(9), e45959 (2012).
   Google Scholar
• 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 7(11), e50976 (2012).
   Google Scholar
• Brooks-Wilson A, Marcil M, Clee SM et al. Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency.Nat. Genet. 22(4), 336–345 (1999).
   Google Scholar
• Karasinska JM, Rinninger F, Lutjohann D et al. Specific loss of brain ABCA1 increases brain cholesterol uptake and influences neuronal structure and function. J. Neurosci. 29(11), 3579–3589 (2009).
   Google Scholar
• Singh-Manoux A, Gimeno D, Kivimaki M, Brunner E, Marmot MG. Low HDL cholesterol is a risk factor for deficit and decline in memory in midlife: the Whitehall II study. Arterioscler. Thromb. Vasc. Biol. 28(8), 1556–1562 (2008).
   Google Scholar
• Chu LW, Li Y, Li Z et al. A novel intronic polymorphism of ABCA1 gene reveals risk for sporadic Alzheimer’s disease in Chinese. Am. J. Med. Genet. B Neuropsychiatr. Genet. 144B(8), 1007–1013 (2007).
   Google Scholar
• Rodriguez-Rodriguez E, Mateo I, Llorca J et al. Association of genetic variants of ABCA1 with Alzheimer’s disease risk. Am. J. Med. Genet. B Neuropsychiatr. Genet. 144B(7), 964–968 (2007).
   Google Scholar
• Wahrle SE, Jiang H, Parsadanian M et al. Deletion of Abca1 increases Abeta deposition in the PDAPP transgenic mouse model of Alzheimer disease. J. Biol. Chem. 280(52), 43236–43242 (2005).
   Google Scholar
• Koldamova R, Staufenbiel M, Lefterov I. Lack of ABCA1 considerably decreases brain ApoE level and increases amyloid deposition in APP23 mice. J. Biol. Chem. 280(52), 43224–43235 (2005).
   Google Scholar
• Hirsch-Reinshagen V, Maia LF, Burgess BL et al. The absence of ABCA1 decreases soluble ApoE levels but does not diminish amyloid deposition in two murine models of Alzheimer disease. J. Biol. Chem. 280(52), 43243–43256 (2005).
   Google Scholar
• Wahrle SE, Jiang H, Parsadanian M et al. Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease. J. Clin. Invest. 118(2), 671–682 (2008).
   Google Scholar
• Burns MP, Vardanian L, Pajoohesh-Ganji A et al. The effects of ABCA1 on cholesterol efflux and Abeta levels in vitro and in vivo. J. Neurochem. 98(3), 792–800 (2006).
   Google Scholar
• Cramer PE, Cirrito JR, Wesson DW et al. ApoE-directed therapeutics rapidly clear beta-amyloid and reverse deficits in AD mouse models. Science 335(6075), 1503–1506 (2012).
   Google Scholar
• Dietschy JM, Turley SD. Thematic review series: brain lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal.J. Lipid Res. 45(8), 1375–1397 (2004).
   Google Scholar
• Bowman GL, Kaye JA, Moore M, Waichunas D, Carlson NE, Quinn JF. Blood–brain barrier impairment in Alzheimer disease: stability and functional significance.Neurology 68(21), 1809–1814 (2007).
   Google Scholar