The continuing failure of bexarotene in alzheimer's disease mice

Journal of Alzheimer's Disease

Volumn 46, Issue 2, 2015, Pages 471-482

  Balducci, Claudia ^a   Paladini, Alessandra ^a   Micotti, Edoardo ^a   Tolomeo, Daniele ^a   La Vitola, Pietro ^a   Grigoli, Emanuele ^a   Richardson, Jill C ^b   Forloni, Gianluigi ^a  

^a MARIO NEGRI INSTITUTE FOR PHARMACOLOGICAL RESEARCH   (Italy)

^b GLAXOSMITHKLINE   (United Kingdom)

Author keywords

Alzheimer's disease; amyloid ; apolipoprotein E; bexarotene; magnetic resonance imaging; memory; TASTPM mice; therapy

Indexed keywords

APOLIPOPROTEIN E; BEXAROTENE; CD68 ANTIGEN; LIVER X RECEPTOR; ORPHAN NUCLEAR RECEPTOR; RETINOID X RECEPTOR; TETRALIN DERIVATIVE;

ALZHEIMER DISEASE; AMNESIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN ATROPHY; BRAIN SIZE; COGNITION; CONTROLLED STUDY; DEREGULATION; DRUG EFFECT; DRUG TREATMENT FAILURE; ENTORHINAL CORTEX; FEMALE; HIPPOCAMPUS; IN VIVO STUDY; MICROGLIA; MOUSE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PHAGOCYTOSIS; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; TRANSCRIPTION REGULATION; TRANSGENIC MOUSE; TREATMENT DURATION; AGONISTS; ANIMAL; BRAIN; DISEASE MODEL; DRUG EFFECTS; MAZE TEST; METABOLISM; PATHOLOGY; TREATMENT FAILURE;

ALZHEIMER DISEASE; ANIMALS; APOLIPOPROTEINS E; BRAIN; DISEASE MODELS, ANIMAL; FEMALE; MAZE LEARNING; MICE; MICE, TRANSGENIC; MICROGLIA; ORPHAN NUCLEAR RECEPTORS; RETINOID X RECEPTORS; TETRAHYDRONAPHTHALENES; TREATMENT FAILURE;

EID: 84930458042     PISSN: 13872877     EISSN: 18758908     Source Type: Journal    
DOI: 10.3233/JAD-150029     Document Type: Article

References (49)

1. Selkoe D, Mandelkow E, Holtzman D (2012) Deciphering Alzheimer disease. Cold Spring Harb Perspect Med 2, a011460
2. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics. Science 297, 353-356
3. Mawuenyega KG, Sigurdson W, Ovod V, Munsell L, Kasten T, Morris JC, Yarasheski KE, Bateman RJ (2010) Decreased clearance of CNS beta-Amyloid in Alzheimer's disease. Science 330, 1774
4. Jiang Q, Lee CY, Mandrekar S, Wilkinson B, Cramer P, Zelcer N, Mann K, Lamb B, Willson TM, Collins JL, Richardson JC, Smith JD, Comery TA, Riddell D, Holtzman DM, Tontonoz P, Landreth GE (2008) ApoE promotes the proteolytic degradation of Abeta. Neuron 58, 681-693
5. Kanekiyo T, Xu H, Bu G (2014) ApoE and Abeta in Alzheimer's disease: Accidental encounters or partners?. Neuron 81, 740-754
6. Harold D, Abraham R, Hollingworth P, Sims R, Gerrish A, Hamshere ML, Pahwa JS, Moskvina V, Dowzell K, Williams A, Jones N, Thomas C, Stretton A, Morgan AR, Lovestone S, Powell J, Proitsi P, Lupton MK, Brayne C, Rubinsztein DC, Gill M, Lawlor B, Lynch A, Morgan K, Brown KS, Passmore PA, Craig D, McGuinness B, Todd S, Holmes C, Mann D, Smith AD, Love S, Kehoe PG, Hardy J, Mead S, Fox N, Rossor M, Collinge J, Maier W, Jessen F, Schurmann B, Heun R, van den Bussche H, Heuser I, Kornhuber J, Wiltfang J, Dichgans M, Frolich L, Hampel H, Hull M, Rujescu D, Goate AM, Kauwe JS, Cruchaga C, Nowotny P, Morris JC, Mayo K, Sleegers K, Bettens K, Engelborghs S, De Deyn PP, Van Broeckhoven C, Livingston G, Bass NJ, Gurling H, McQuillin A, Gwilliam R, Deloukas P, Al-Chalabi A, Shaw CE, Tsolaki M, Singleton AB, Guerreiro R, Muhleisen TW, NothenMM, Moebus S, Jockel KH, Klopp N, Wichmann HE, Carrasquillo MM, Pankratz VS, Younkin SG, Holmans PA, O'Donovan M, Owen MJ, Williams J (2009) Genomewide association study identifies Variants at CLU and PICALM associated with Alzheimer's disease. Nat Genet 41, 1088-1093
7. Lambert JC, Heath S, Even G, Campion D, Sleegers K, Hiltunen M, Combarros O, Zelenika D, Bullido MJ, Tavernier B, Letenneur L, Bettens K, Berr C, Pasquier F, Fievet N, Barberger-Gateau P, Engelborghs S, De Deyn P, Mateo I, Franck A, Helisalmi S, Porcellini E, Hanon O, de Pancorbo MM, Lendon C, Dufouil C, Jaillard C, Leveillard T, Alvarez V, Bosco P, Mancuso M, Panza F, Nacmias B, Bossu P, Piccardi P, Annoni G, Seripa D, Galimberti D, Hannequin D, Licastro F, Soininen H, Ritchie K, Blanche H, Dartigues JF, Tzourio C, Gut I, Van BroeckhovenC, Alperovitch A, Lathrop M, Amouyel P (2009) Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Nat Genet 41, 1094-1099
8. Russo C, Angelini G, Dapino D, Piccini A, Piombo G, Schettini G, Chen S, Teller JK, Zaccheo D, Gambetti P, Tabaton M (1998) Opposite roles of apolipoprotein E in normal brains and in Alzheimer's disease. Proc Natl Acad Sci U S A 95, 15598-15602
9. Tokuda T, Calero M, Matsubara E, Vidal R, Kumar A, Permanne B, Zlokovic B, Smith JD, Ladu MJ, Rostagno A, Frangione B, Ghiso J (2000) Lipidation of apolipoprotein E influences its isoform-specific interaction with Alzheimer's amyloid beta peptides. Biochem J 348 Pt 2, 359-365
10. Cramer PE, Cirrito JR, Wesson DW, Lee CY, Karlo JC, Zinn AE, Casali BT, Restivo JL, Goebel WD, James MJ, Brunden KR, WilsonDA, LandrethGE(2012) ApoE-directed therapeutics rapidly clear beta-Amyloid and reverse deficits in AD mouse models. Science 335, 1503-1506
11. Tai LM, Koster KP, Luo J, Lee SH, Wang YT, Collins NC, Ben Aissa M, Thatcher GR, LaDu MJ (2014) Amyloid-beta pathology and APOE genotype modulate retinoid X receptor agonist activity in vivo. J Biol Chem 289, 30538-30555
12. Fitz NF, Cronican AA, Lefterov I, Koldamova R (2013) Comment on "ApoE-directed therapeutics rapidly clear betaamyloid and reverse deficits in AD mouse models". Science 340, 924-c.
13. Price AR, Xu G, Siemienski ZB, Smithson LA, Borchelt DR, Golde TE, Felsenstein KM (2013) Comment on "ApoEdirected therapeutics rapidly clear beta-Amyloid and reverse deficits in AD mouse models". Science 340, 924-d.
14. Tesseur I, Lo AC, Roberfroid A, Dietvorst S, Van Broeck B, Borgers M, Gijsen H, Moechars D, Mercken M, Kemp J, D'Hooge R, De Strooper B (2013) Comment on "ApoEdirected therapeutics rapidly clear beta-Amyloid and reverse deficits in AD mouse models". Science 340, 924-e.
15. Veeraraghavalu K, Zhang C, Miller S, Hefendehl JK, Rajapaksha TW, Ulrich J, Jucker M, Holtzman DM, Tanzi RE, Vassar R, Sisodia SS (2013) Comment on "ApoE-directed therapeutics rapidly clear beta-Amyloid and reverse deficits in AD mouse models". Science 340, 924-f.
16. Micotti E, Paladini A, Balducci C, Tolomeo D, Frasca A, Marizzoni M, Filibian M, Caroli A, Valbusa G, Dix S, O'Neill M, Ozmen L, Czech C, Richardson JC, Frisoni GB, Forloni G (2015) Striatum and entorhinal cortex atrophy in AD mouse models: MRI comprehensive analysis. Neurobiol Aging 36, 776-788
17. Balducci C, Beeg M, Stravalaci M, Bastone A, Sclip A, Biasini E, Tapella L, Colombo L, Manzoni C, Borsello T, Chiesa R, Gobbi M, Salmona M, Forloni G (2010) Synthetic amyloid-beta oligomers impair long-term memory independently of cellular prion protein. Proc Natl Acad Sci U S A 107, 2295-2300
18. Balducci C, Forloni G (2014) In vivo application of beta amyloid oligomers: A simple tool to evaluate mechanisms of action and new therapeutic approaches. Curr Pharm Des 20, 2491-2505
19. Balducci C, Mancini S, Minniti S, La Vitola P, Zotti M, Sancini G, Mauri M, Cagnotto A, Colombo L, Fiordaliso F, Grigoli E, Salmona M, Snellman A, Haaparanta-Solin M, Forloni G, Masserini M, Re F (2014) Multifunctional liposomes reduce brain beta-Amyloid burden and ameliorate memory impairment in Alzheimer's disease mouse models. J Neurosci 34, 14022-14031
20. Balducci C, Mehdawy B, Mare L, Giuliani A, Lorenzini L, Sivilia S, Giardino L, Calza L, Lanzillotta A, Sarnico I, Pizzi M, Usiello A, Viscomi AR, Ottonello S, Villetti G, Imbimbo BP, Nistico G, Forloni G, Nistico R (2011) The gamma-secretase modulator CHF5074 restores memory and hippocampal synaptic plasticity in plaque-free Tg2576 mice. J Alzheimers Dis 24, 799-816
21. Baitsch D, Bock HH, Engel T, Telgmann R, Muller-Tidow C, VargaG, Bot M, Herz J, Robenek H, von Eckardstein A, Nofer JR Apolipoprotein E induces antiinflammatory phenotype in macrophages. Arterioscler Thromb Vasc Biol 31, 1160-1168
22. Aguzzi A, Barres BA, Bennett ML (2013) Microglia: Scapegoat, saboteur, or something else?. Science 339, 156-161
23. Howlett DR, Richardson JC, Austin A, Parsons AA, Bate ST, Davies DC, GonzalezMI(2004) Cognitive correlates of Abeta deposition in male and female mice bearing amyloid precursor protein and presenilin-1 mutant transgenes. Brain Res 1017, 130-136
24. Franklin KBJ, Paxinos G (1997) The Mouse Brain in Stereotaxic Coordinates, Elsevier, London.
25. Yang D, Xie Z, Stephenson D, Morton D, Hicks CD, Brown TM, Sriram R, O'Neill S, Raunig D, Bocan T (2011) Volumetric MRI and MRS provide sensitive measures of Alzheimer's disease neuropathology in inducible Tau transgenic mice (rTg4510). Neuroimage 54, 2652-2658
26. Antunes M, Biala G (2012) The novel object recognition memory: Neurobiology, test procedure, and its modifications. Cogn Process 13, 93-110
27. Ravizza T, Gagliardi B, Noe F, Boer K, Aronica E, Vezzani A (2008) Innate and adaptive immunity during epileptogenesis and spontaneous seizures: Evidence from experimental models and human temporal lobe epilepsy. Neurobiol Dis 29, 142-160
28. Balducci C, Tonini R, Zianni E, Nazzaro C, Fiordaliso F, Salio M, Vismara L, Gardoni F, Di Luca M, Carli M, ForloniG (2010) Cognitive deficits associated with alteration of synaptic metaplasticity precede plaque deposition in AbetaPP23 transgenic mice. J Alzheimers Dis 21, 1367-1381
29. Zanier ER, Montinaro M, Vigano M, Villa P, Fumagalli S, Pischiutta F, Longhi L, Leoni ML, Rebulla P, Stocchetti N, Lazzari L, De Simoni MG (2011) Human umbilical cord blood mesenchymal stem cells protect mice brain after trauma. Crit Care Med 39, 2501-2510
30. Fox NC, Black RS, Gilman S, Rossor MN, Griffith SG, Jenkins L, Koller M (2005) Effects of Abeta immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease. Neurology 64, 1563-1572
31. LaClair KD, Manaye KF, Lee DL, Allard JS, Savonenko AV, Troncoso JC, Wong PC (2013) Treatment with bexarotene, a compound that increases apolipoprotein-E, provides no cognitive benefit in mutant APP/PS1 mice. Mol Neurodegener 8, 18
32. Odegaard JI, Chawla A (2011) Alternative macrophage activation and metabolism. Annu Rev Pathol 6, 275-297
33. Mandrekar-Colucci S, Landreth GE (2011) Nuclear receptors as therapeutic targets for Alzheimer's disease. Expert Opin Ther Targets 15, 1085-1097
34. Micklem K, Rigney E, Cordell J, Simmons D, Stross P, Turley H, Seed B, Mason D (1989) A human macrophageassociated antigen (CD68) detected by six different monoclonal antibodies. Br J Haematol 73, 6-11
35. Ramprasad MP, Terpstra V, Kondratenko N, Quehenberger O, Steinberg D (1996) Cell surface expression of mouse macrosialin and human CD68 and their role as macrophage receptors for oxidized lowdensity lipoprotein. Proc Natl Acad Sci U S A 93, 14833-14838
36. Holness CL, Simmons DL (1993) Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins. Blood 81, 1607-1613
37. Travaglione S, Falzano L, Fabbri A, Stringaro A, Fais S, Fiorentini C (2002) Epithelial cells and expression of the phagocytic marker CD68: Scavenging of apoptotic bodies following Rho activation. Toxicol In Vitro 16, 405-411
38. Kuo YM, Emmerling MR, Vigo-Pelfrey C, Kasunic TC, Kirkpatrick JB, Murdoch GH, Ball MJ, Roher AE (1996) Water-soluble Abeta (N-40, N-42) oligomers in normal and Alzheimer disease brains. J Biol Chem 271, 4077-4081
39. McLean CA, Cherny RA, Fraser FW, Fuller SJ, Smith MJ, Beyreuther K, Bush AI, Masters CL (1999) Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease. Ann Neurol 46, 860-866
40. Mucke L, Selkoe DJ (2012) Neurotoxicity of amyloid betaprotein: Synaptic and network dysfunction. Cold Spring Harb Perspect Med 2, a006338
41. Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS, Rowan MJ, Selkoe DJ (2002) Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416, 535-539
42. Cai XD, Golde TE, Younkin SG (1993) Release of excess amyloid beta protein from a mutant amyloid beta protein precursor. Science 259, 514-516
43. Bomben V, Holth J, Reed J, Cramer P, Landreth G, Noebels J (2012) Bexarotene reduces network excitability in models of Alzheimer's disease and epilepsy. Neurobiol Aging 35, 2091-2095
44. Simeone TA, Simeone KA, Samson KK, Kim do Y, Rho JM (2013) Loss of the Kv1.1 potassium channel promotes pathologic sharp waves and high frequency oscillations in in vitro hippocampal slices. Neurobiol Dis 54, 68-81
45. Di Scala C, Troadec JD, Lelievre C, Garmy N, Fantini J, Chahinian H Mechanism of cholesterol-Assisted oligomeric channel formation by a short Alzheimer beta-Amyloid peptide. J Neurochem 128, 186-195
46. Fantini J, Di Scala C, Yahi N, Troadec JD, Sadelli K, Chahinian H, Garmy N (2014) Bexarotene blocks calciumpermeable ion channels formed by neurotoxic Alzheimer's beta-Amyloid peptides. ACS Chem Neurosci 5, 216-224
47. Youmans KL, Tai LM, Nwabuisi-Heath E, Jungbauer L, Kanekiyo T, Gan M, Kim J, Eimer WA, Estus S, Rebeck GW, Weeber EJ, Bu G, Yu C, Ladu MJ (2012) APOE4-specific changes in Abeta accumulation in a new transgenic mouse model of Alzheimer disease. J Biol Chem 287, 41774-41786
48. Boehm-Cagan A, MichaelsonDM(2014) Reversal of apoE4-driven brain pathology and behavioral deficits by bexarotene. J Neurosci 34, 7293-7301
49. Aicardi G (2013) New hope from an old drug: Fighting Alzheimer's disease with the cancer drug bexarotene (targretin)?. Rejuvenation Res 16, 524-528v