β-site amyloid precursor protein-cleaving enzyme 1(BACE1) inhibitor treatment induces Aβ5-X peptides through alternative amyloid precursor protein cleavage

Alzheimer's Research and Therapy

Volumn 6, Issue 9, 2014, Pages

  Portelius, Erik ^a   Dean, Robert A ^b   Andreasson, Ulf ^a   Mattsson, Niklas ^a,c   Westerlund, Anni ^a   Olsson, Maria ^a   Demattos, Ronald Bradley ^b   Racke, Margaret M ^b   Zetterberg, Henrik ^a,d   May, Patrick C ^b   Blennow, Kaj ^a  

^a UNIVERSITY OF GOTHENBURG   (Sweden)

^b ELI LILLY AND COMPANY   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN [1-34]; AMYLOID BETA PROTEIN[5-40]; AMYLOID BETA PROTEIN[5-X]; AMYLOID PRECURSOR PROTEIN; BETA SECRETASE 1; BETA SECRETASE INHIBITOR; BIOLOGICAL MARKER; LY 2811376; UNCLASSIFIED DRUG;

ADULT; ARTICLE; CEREBROSPINAL FLUID LEVEL; CONTROLLED STUDY; DOSE RESPONSE; DRUG EFFECT; DRUG MECHANISM; DRUG TARGETING; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; HUMAN; HUMAN EXPERIMENT; IMMUNOAFFINITY CHROMATOGRAPHY; MALE; MATRIX ASSISTED LASER DESORPTION IONIZATION TIME OF FLIGHT MASS SPECTROMETRY; NEUROBLASTOMA CELL LINE; NORMAL HUMAN; PRIORITY JOURNAL; PROTEIN CLEAVAGE; RANDOMIZED CONTROLLED TRIAL; SINGLE BLIND PROCEDURE; SINGLE DRUG DOSE;

EID: 84920857677     PISSN: None     EISSN: 17589193     Source Type: Journal    
DOI: 10.1186/s13195-014-0075-0     Document Type: Article

References (28)

1. Glenner GG, Wong CW: Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 1984, 120:885-890.
2. Hardy J, Allsop D: Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends Pharmacol Sci 1991, 12:383-388.
3. Vassar R, Kandalepas PC: The beta-secretase enzyme BACE1 as a therapeutic target for Alzheimer's disease. Alzheimers Res Ther 2011, 3:20.
4. Steiner H, Fluhrer R, Haass C: Intramembrane proteolysis by gamma-secretase. J Biol Chem2008, 283:29627-29631.
5. Citron M: Alzheimer's disease: strategies for disease modification. Nat Rev Drug Discov 2010, 9:387-398.
6. Blennow K, Hampel H, Weiner M, Zetterberg H: Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol 2010, 6:131-144.
7. Portelius E, Andreasson U, Ringman JM, Buerger K, Daborg J, Buchhave P, Hansson O, Harmsen A, Gustavsson MK, Hanse E, Galasko D, Hampel H, Blennow K, Zetterberg H: Distinct cerebrospinal fluid amyloid beta peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease. Mol Neurodegener 2010, 5:2.
8. Pannee J, Portelius E, Oppermann M, Atkins A, Hornshaw M, Zegers I, Hojrup P, Minthon L, Hansson O, Zetterberg H, Blennow K, Gobom J: A Selected Reaction Monitoring (SRM)-based method for absolute quantification of Abeta38, Abeta40, and Abeta42 in cerebrospinal fluid of Alzheimer's disease patients and healthy controls. J Alzheimers Dis 2013, 33:1021-1032.
9. Mattsson N, Rajendran L, Zetterberg H, Gustavsson M, Andreasson U, Olsson M, Brinkmalm G, Lundkvist J, Jacobson LH, Perrot L, Neumann U, Borghys H, Mercken M, Dhuyvetter D, Jeppsson F, Blennow K, Portelius E: BACE1 inhibition induces a specific cerebrospinal fluid beta-amyloid pattern that identifies drug effects in the central nervous system. PLoS One 2012, 7:e31084.
10. Portelius E, Price E, Brinkmalm G, Stiteler M, Olsson M, Persson R, Westman- Brinkmalm A, Zetterberg H, Simon AJ, Blennow K: A novel pathway for amyloid precursor protein processing. Neurobiol Aging 2011, 32:1090-1098.
11. Cook JJ, Wildsmith KR, Gilberto DB, Holahan MA, Kinney GG, Mathers PD, Michener MS, Price EA, Shearman MS, Simon AJ, Wang JX, Wu G, Yarasheski KE, Bateman RJ: Acute gamma-secretase inhibition of nonhuman primate CNS shifts amyloid precursor protein (APP) metabolism from amyloid-beta production to alternative APP fragments without amyloid-beta rebound. J Neurosci 2010, 30:6743-6750.
12. Portelius E, Van Broeck B, Andreasson U, Gustavsson MK, Mercken M, Zetterberg H, Borghys H, Blennow K: Acute effect on the Abeta isoform pattern in CSF in response to gamma-secretase modulator and inhibitor treatment in dogs. J Alzheimers Dis 2010, 21:1005-1012.
13. Kuhn PH, Wang H, Dislich B, Colombo A, Zeitschel U, Ellwart JW, Kremmer E, Rossner S, Lichtenthaler SF: ADAM10 is the physiologically relevant, constitutive alpha-secretase of the amyloid precursor protein in primary neurons. EMBO J 2010, 29:3020-3032.
14. Coric V, van Dyck CH, Salloway S, Andreasen N, Brody M, Richter RW, Soininen H, Thein S, Shiovitz T, Pilcher G, Colby S, Rollin L, Dockens R, Pachai C, Portelius E, Andreasson U, Blennow K, Soares H, Albright C, Feldman HH, Berman RM: Safety and tolerability of the gamma-secretase inhibitor avagacestat in a phase 2 study of mild to moderate alzheimer disease. Arch Neurol 2012, 69:1430-1440.
15. Portelius E, Dean RA, Gustavsson MK, Andreasson U, Zetterberg H, Siemers E, Blennow K: A novel Abeta isoform pattern in CSF reflects gamma-secretase inhibition in Alzheimer disease. Alzheimers Res Ther 2010, 2:7.
16. Portelius E, Zetterberg H, Dean RA, Marcil A, Bourgeois P, Nutu M, Andreasson U, Siemers E, Mawuenyega KG, Sigurdson WC, May PC, Paul SM, Holtzman DM, Blennow K, Bateman RJ: Amyloid-beta(1-15/16) as a marker for gamma-secretase inhibition in Alzheimer's disease. J Alzheimers Dis 2012, 31:335-341.
17. May PC, Dean RA, Lowe SL, Martenyi F, Sheehan SM, Boggs LN, Monk SA, Mathes BM, Mergott DJ, Watson BM, Stout SL, Timm DE, Smith Labell E, Gonzales CR, Nakano M, Jhee SS, Yen M, Ereshefsky L, Lindstrom TD, Calligaro DO, Cocke PJ, Greg Hall D, Friedrich S, Citron M, Audia JE: Robust central reduction of amyloid-beta in humans with an orally available, non-peptidic beta-secretase inhibitor. J Neurosci 2011, 31:16507-16516.
18. Portelius E, Tran AJ, Andreasson U, Persson R, Brinkmalm G, Zetterberg H, Blennow K, Westman-Brinkmalm A: Characterization of amyloid beta peptides in cerebrospinal fluid by an automated immunoprecipitation procedure followed by mass spectrometry. J Proteome Res 2007, 6:4433-4439.
19. Biedler JL, Roffler-Tarlov S, Schachner M, Freedman LS: Multiple neurotransmitter synthesis by human neuroblastoma cell lines and clones. Cancer Res 1978, 38:3751-3757.
20. Stachel SJ, Coburn CA, Steele TG, Jones KG, Loutzenhiser EF, Gregro AR, Rajapakse HA, Lai MT, Crouthamel MC, Xu M, Tugusheva K, Lineberger JE, Pietrak BL, Espeseth AS, Shi XP, Chen-Dodson E, Holloway MK, Munshi S, Simon AJ, Kuo L, Vacca JP: Structure-based design of potent and selective cell-permeable inhibitors of human beta-secretase (BACE-1). J Med Chem 2004, 47:6447-6450.
21. Johnson-Wood K, Lee M, Motter R, Hu K, Gordon G, Barbour R, Khan K, Gordon M, Tan H, Games D, Lieberburg I, Schenk D, Seubert P, McConlogue L: Amyloid precursor protein processing and A beta42 deposition in a transgenic mouse model of Alzheimer disease. Proc Natl Acad Sci U S A 1997, 94:1550-1555.
22. Seubert P, Vigo-Pelfrey C, Esch F, Lee M, Dovey H, Davis D, Sinha S, Schlossmacher M, Whaley J, Swindlehurst C, McCormack R, Wolfert R, Selkoe D, Lieberburg I, Schenk D: Isolation and quantification of soluble Alzheimer's beta-peptide from biological fluids. Nature 1992, 359:325-327.
23. Atwal JK, Chen Y, Chiu C, Mortensen DL, Meilandt WJ, Liu Y, Heise CE, Hoyte K, Luk W, Lu Y, Peng K, Wu P, Rouge L, Zhang Y, Lazarus RA, Scearce-Levie K, Wang W, Wu Y, Tessier-Lavigne M, Watts RJ: A therapeutic antibody targeting BACE1 inhibits amyloid-beta production in vivo. Sci Transl Med 2011, 3:84ra43.
24. Takeda K, Araki W, Akiyama H, Tabira T: Amino-truncated amyloid betapeptide (Abeta5-40/42) produced from caspase-cleaved amyloid precursor protein is deposited in Alzheimer's disease brain. FASEB J 2004, 18:1755-1757.
25. Miners JS, Barua N, Kehoe PG, Gill S, Love S: Abeta-degrading enzymes: potential for treatment of Alzheimer disease. J Neuropathol Exp Neurol 2011, 70:944-959.
26. Fluhrer R, Multhaup G, Schlicksupp A, Okochi M, Takeda M, Lammich S, Willem M, Westmeyer G, Bode W, Walter J, Haass C: Identification of a beta-secretase activity, which truncates amyloid beta-peptide after its presenilin-dependent generation. J Biol Chem 2003, 278:5531-5538.
27. Shi XP, Tugusheva K, Bruce JE, Lucka A, Wu GX, Chen-Dodson E, Price E, Li Y, Xu M, Huang Q, Sardana MK, Hazuda DJ: Beta-secretase cleavage at amino acid residue 34 in the amyloid beta peptide is dependent upon gamma-secretase activity. J Biol Chem 2003, 278:21286-21294.
28. Portelius E, Bogdanovic N, Gustavsson MK, Volkmann I, Brinkmalm G, Zetterberg H, Winblad B, Blennow K: Mass spectrometric characterization of brain amyloid beta isoform signatures in familial and sporadic Alzheimer's disease. Acta Neuropathol 2010, 120:185-193.