Pyroglutamate-modified amyloid-β protein demonstrates similar properties in an Alzheimer's disease familial mutant knock-in mouse and Alzheimer's disease brain

Neurodegenerative Diseases

Volumn 14, Issue 2, 2014, Pages 53-66

  Wu, Guoxin ^a   Miller, Ronald A ^a   Connolly, Brett ^b   Marcus, Jacob ^a   Renger, John ^a   Savage, Mary J ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

^b Department of Imaging ^*  (United States)

Author keywords

Amyloid precursor protein; Immunoassay; P264L; pE3A ; Presenilin 1; Pyroglutamate

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; GLUTAMIC ACID; PRESENILIN 1; PYROGLUTAMIC ACID; ANTIBODY;

AGE; ALZHEIMER DISEASE; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN; CONTROLLED STUDY; ENZYME LINKED IMMUNOSORBENT ASSAY; GENE MUTATION; GENE OVEREXPRESSION; HUMAN; HUMAN TISSUE; KNOCKOUT MOUSE; MOUSE; NEUROANATOMY; NEUROPATHOLOGY; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN FOLDING; TG2576 MOUSE; ANIMAL EXPERIMENT; BRAIN HOMOGENATE; BRAIN LEVEL; CLINICAL ARTICLE; GENE TARGETING; ANIMAL; CEREBROSPINAL FLUID; CHEMISTRY; DISEASE MODEL; GENETICS; IMMUNOLOGY; METABOLISM; TRANSGENIC MOUSE;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; ANTIBODIES; BRAIN; DISEASE MODELS, ANIMAL; ENZYME-LINKED IMMUNOSORBENT ASSAY; GENE KNOCK-IN TECHNIQUES; HUMANS; MICE; MICE, TRANSGENIC; PRESENILIN-1; PYRROLIDONECARBOXYLIC ACID;

EID: 84906940727     PISSN: 16602854     EISSN: 16602862     Source Type: Journal    
DOI: 10.1159/000353634     Document Type: Article

References (49)

1. Selkoe DJ: Alzheimer's disease results from the cerebral accumulation and cytotoxicity of amyloid β-protein. J Alzheimers Dis 2001; 3: 75-80.
2. Vassar R, Citron M: Aβ-generating enzymes: Recent advances in β-and γ-secretase research. Neuron 2000; 27: 419-422.
3. Saido TC, Iwatsubo T, Mann DM, Shimada H, Ihara Y, Kawashima S: Dominant and differential deposition of distinct β-amyloid peptide species, Aβ N3(pE), in senile plaques. Neuron 1995; 4: 457-466.
4. Iwatsubo T, Saido TC, Mann DM, Lee VM, Trojanowski JQ: Full-length amyloid-beta (1-42(43)) and amino-terminally modified and truncated amyloid-beta 42(43) deposit in diffuse plaques. Am J Pathol 1996; 149: 1823-1830.
5. Kuo YM, Emmerling MR, Woods AS, Cotter RJ, Roher AE: Isolation, chemical characterization, and quantitation of Aβ 3-pyroglutamyl peptide from neuritic plaques and vascular amyloid deposits. Biochem Biophys Res Commun 1995; 237: 188-191.
6. Russo C, Saido TC, DeBusk LM, Tabaton M, Gambetti P, Teller JK: Heterogeneity of water-soluble amyloid β-peptide in Alzheimer's disease and Down's syndrome brains. FEBS Lett 1997; 409: 411-416.
7. Tekirian TL, Saido TC, Markesbery WR, Russell MJ, Wekstein DR, Patel E, Geddes JW: Nterminal heterogeneity of parenchymal and cerebrovascular Aβ deposits. J Neuropathol Exp Neurol 1998; 57: 76-94.
8. Mori H, Ishii K, Tomiyama T, Furiya Y, Sahara N, Asano S, Endo N, Shirasawa T, Takio K: Racemization: Its biological significance on neuropathogenesis of Alzheimer's disease. Tohoku J Exp Med 1994; 174: 251-262.
9. Harigaya Y, Saido TC, Eckman CB, Prada CM, Shoji M, Younkin SG: Amyloid-β protein starting pyroglutamate at position 3 is a major component of the amyloid deposits in the Alzheimer's disease brain. Biochem Biophys Res Commun 2000; 276: 422-427.
10. Miravalle L, Calero M, Takao M, Roher AE, Ghetti B, Vidal R: Amino-terminally truncated Aβ peptide species are the main component of cotton wool plaques. Biochem 2005; 44: 10810-10821.
11. Piccini A, Russo C, Gliozzi A, Relini A, Vitali A, Borghi R, Giliberto L, Armirotti A, D'Arrigo C, Bachi A, Cattaneo A, Canale C, Torrassa S, Saido TC, Markesbery W, Gambetti P, Tabaton M: Beta;-Amyloid is different in normal aging and in Alzheimer disease. J Biol Chem 2005; 280: 34186-34192.
12. Schilling S, Zeitschel U, Hoffmann T, Heiser U, Francke M, Kehlen A, Holzer M, Hutter-Paier B, Prokesch M, Windisch M, Jagla W, Schlenzig D, Lindner C, Rudolph T, Reuter G, Cynis H, Montag D, Demuth HU, Rossner S: Glutaminyl cyclase inhibition attenuates pyroglutamate Aβ and Alzheimer's disease-like pathology. Nat Med 2008; 14: 1106-1111.
13. Hosoda R, Saido TC, Otvos L Jr, Arai T, Mann DM, Lee VM, Trojanowski JQ, Iwatsubo T: Quantification of modified amyloid-β peptides in Alzheimer disease and Down syndrome brains. J Neuropathol Exp Neurol 1998; 57: 1089-1095.
14. He W, Barrow CJ: The Aβ 3-pyroglutamyl and 11-pyroglutamyl peptides found in senile plaque have greater β-sheet forming and aggregation propensities in vitro than fulllength Aβ. Biochemistry 1999; 38: 10871-10877.
15. D'Arrigo C, Tabaton M, Perico A: N-terminal truncated pyroglutamyl β-amyloid peptide Aβpy3-42 shows faster aggregation kinetics than the full-length Aβ1-42. Biopolymers 2009; 91: 861-873.
16. Schilling S, Appl T, Hoffmann T, Cynis H, Schulz K, Jagla W, Friedrich D, Wermann M, Buchholz M, Heiser U, von Hörsten S, Demuth HU: Inhibition of glutaminyl cyclase prevents pGlu-Aβ formation after intracortical/ hippocampal microinjection in vivo/in situ. J Neurochem 2008b;106: 1225-1236.
17. Schlenzig D, Manhart S, Cinar Y, Kleinschmidt M, Hause G, Willbold D, Funke SA, Schilling S, Demuth HU: Pyroglutamate formation influences solubility and amyloidogenicity of amyloid peptides. Biochemistry 2009; 48: 7072-7078.
18. Russo C, Salis S, Dolcini V, Venezia V, Song XH, Teller JK, Schettini G: Identification of amino-terminally and phosphotyrosinemodified carboxy-terminal fragments of the amyloid precursor protein in Alzheimer's disease and Down's syndrome brain. Neurobiol Dis 2001; 8: 173-180.
19. Jawhar S, Trawicka A, Jenneckens C, Bayer TA, Wirths O: Motor deficits, neuron loss, and reduced anxiety coinciding with axonal degeneration and intraneuronal Aβ aggregation in the 5XFAD mouse model of Alzheimer's disease. Neurobiol Aging 2012; 33: 196. e29-e40.
20. Jawhar S, Wirths O, Bayer TA: Pyroglutamate amyloid-β (Aβ): A hatchet man in Alzheimer disease. J Biol Chem 2011; 286: 38825-38832.
21. Oakley H, Cole SL, Logan S, Maus E, Shao P, Craft J, Guillozet-Bongaarts A, Ohno M, Disterhoft J, Van Eldik L, Berry R, Vassar R: Intraneuronal β-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer's disease mutations: Potential factors in amyloid plaque formation. J Neurosci 2006; 26: 10129-10140.
22. Casas C, Sergeant N, Itier JM, Blanchard V, Wirths O, van der Kolk N, Vingtdeux V, van de Steeg E, Ret G, Canton T, Drobecq H, Clark A, Bonici B, Delacourte A, Benavides J, Schmitz C, Tremp G, Bayer TA, Benoit P, Pradier L: Massive CA1/2 neuronal loss with intraneuronal and N-terminal truncated Aβ42 accumulation in a novel Alzheimer transgenic model. Am J Pathol 2004; 165: 1289-1300.
23. Wirths O, Bethge T, Marcello A, Harmeier A, Jawhar S, Lucassen PJ, Multhaup G, Brody DL, Esparza T, Ingelsson M, Kalimo H, Lannfelt L, Bayer TA: Pyroglutamate Aβ pathology in APP/PS1KI mice, sporadic and familial Alzheimer's disease cases. J Neural Transm 2010; 117: 85-96.
24. Flood DG, Reaume AG, Dorfman KS, Lin YG, Lang DM, Trusko SP, Savage MJ, Annaert WG, De Strooper B, Siman R, Scott RW: FAD mutant PS-1 gene-targeted mice: Increased Aβ42 and Aβ deposition without APP overproduction. Neurobiol Aging 2002; 23: 335-348.
25. Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G: Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice. Science 1996; 274: 99-102.
26. Wu G, Sankaranarayanan S, Tugusheva K, Kahana J, Seabrook G, Shi XP: Decrease in age-adjusted cerebrospinal fluid β-secretase activity in Alzheimer's subjects. Clin Biochem 2008; 41: 986-996.
27. Wu G, Sankaranarayanan S, Montgomery DL, Simon AJ, An Z, Savage MJ: Pharmacological applications of a novel neoepitope antibody to a modified amyloid precursor protein-derived β-secretase substrate. Protein Cell 2011; 2: 573-584.
28. Sankaranarayanan S, Price EA, Wu G, Crouthamel MC, Shi XP, Tugusheva K, Tyler KX, Kahana J, Ellis J, Jin L, Steele T, Stachel S, Coburn C, Simon AJ: In vivo β-secretase 1 inhibition leads to brain Aβ lowering and increased α-secretase processing of amyloid precursor protein without effect on neuregulin-1. J Pharmacol Exp Ther 2008; 324: 957-969.
29. Wu G, Sankaranarayanan S, Hsieh S, Simon AJ, Savage MJ: Decrease in brain-soluble amyloid precursor protein β (sAPPβ) in Alzheimer's disease cortex. J Neurosci Res 2011; 89: 822-832.
30. Wu G, Sankaranarayanan S, Wong J, Tugusheva K, Michener MS, Shi XP, Cook JJ, Simon AJ, Savage MJ: Characterization of plasma β-secretase (BACE1) activity and soluble amyloid precursor proteins as potential biomarkers for Alzheimer's disease. J Neurosci Res 2012; 90: 2247-2258.
31. Siman R, Reaume AG, Savage MJ, Trusko S, Lin YG, Scott RW, Flood DG: Presenilin-1 P264L knock-in mutation: differential effects on Aβ production, amyloid deposition, and neuronal vulnerability. J Neurosci 2000; 20: 8717-8726.
32. Zheng H, Jiang M, Trumbauer ME, Sirinathsinghji DJ, Hopkins R, Smith DW, Heavens RP, Dawson GR, Boyce S, Conner MW, Stevens KA, Slunt HH, Sisoda SS, Chen HY, Van der Ploeg LH: β-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. Cell 1995; 81: 525-531.
33. Savage MJ, Trusko SP, Howland DS, Pinsker LR, Mistretta S, Reaume AG, Greenberg BD, Siman R, Scott RW: Turnover of amyloid β-protein in mouse brain and acute reduction of its level by phorbol ester. J Neurosci 1998; 18: 1743-1752.
34. Petanceska SS, Nagy V, Frail D, Gandy S: Ovariectomy and 17β-estradiol modulate the levels of Alzheimer's amyloid-β peptides in brain. Neurology 2000; 54: 2212-2217.
35. Eckman EA, Watson M, Marlow L, Sambamurti K, Eckman CB: Alzheimer's disease β-amyloid peptide is increased in mice deficient in endothelin-converting enzyme. J Biol Chem 2003; 278: 2081-2094.
36. Best JD, Smith DW, Reilly MA, O'Donnell R, Lewis HD, Ellis S, Wilkie N, Rosahl TW, Laroque PA, Boussiquet-Leroux C, Churcher I, Atack JR, Harrison T, Shearman MS: The novel γ-secretase inhibitor N-[cis-4-[(4-chlorophenyl) sulfonyl]-4-(2, 5-difluorophenyl) cyclohexyl]-1, 1, 1- trifluoromethanesulfonamide (MRK-560) reduces amyloid plaque deposition without evidence of notch-related pathology in the Tg2576 mouse. J Pharmacol Exp Ther 2007; 320: 552-558.
37. Nolan RL, Teller JK: Diethylamine extraction of proteins and peptides isolated with a mono-phasic solution of phenol and guanidine isothiocyanate. J Biochem Biophys Methods 2006; 68: 127-131.
38. Kawarabayashi T, Younkin LH, Saido TC, Shoji M, Ashe KH, Younkin SG: Age-dependent changes in brain, CSF, and plasma amyloid-β protein in the Tg2576 transgenic mouse model of Alzheimer's disease. J Neurosci 2001; 21: 372-381.
39. Maeda J, Zhang MR, Okauchi T, Ji B, Ono M, Hattori S, Kumata K, Iwata N, Saido TC, Trojanowski JQ, Lee VM, Staufenbiel M, Tomiyama T, Mori H, Fukumura T, Suhara T, Higuchi M: In vivo positron emission tomographic imaging of glial responses to amyloid-β and tau pathologies in mouse models of Alzheimer's disease and related disorders. J Neurosci 2011; 31: 4720-4730.
40. Demattos RB, Lu J, Tang Y, Racke MM, Delong CA, Tzaferis JA, Hole JT, Forster BM, McDonnell PC, Liu F, Kinley RD, Jordan WH, Hutton M: A plaque-specific antibody clears existing β-amyloid plaques in Alzheimer's disease mice. Neuron 2012; 76: 908-920.
41. Mori H, Takio K, Ogawara M, Selkoe DJ: Mass spectrometry of purified amyloid-β protein in Alzheimer's disease. J Biol Chem 1992; 267: 17082-17086.
42. Portelius E, Bogdanovic N, Gustavsson MK, Volkmann I, Brinkmalm G, Zetterberg H, Winblad B, Blennow K: Mass spectrometric characterization of brain amyloid-β isoform signatures in familial and sporadic Alzheimer's disease. Acta Neuropathol 2010; 120: 185-193.
43. Wirths O, Breyhan H, Cynis H, Schilling S, Demuth HU, Bayer TA: Intraneuronal pyroglutamate-Aβ3-42 triggers neurodegeneration and lethal neurological deficits in a transgenic mouse model. Acta Neuropathol 2009; 118: 487-496.
44. Alexandru A, Jagla W, Graubner S, Becker A, Bäuscher C, Kohlmann S, Sedlmeier R, Raber KA, Cynis H, Rönicke R, Reymann KG, Petrasch-Parwez E, Hartlage-Rübsamen M, Waniek A, Rossner S, Schilling S, Osmand AP, Demuth HU, von Hörsten S: Selective hippocampal neurodegeneration in transgenic mice expressing small amounts of truncated Aβ is induced by pyroglutamate-Aβ formation. J Neurosci 2011; 31: 12790-12801.
45. Chang EH, Savage MJ, Flood DG, Thomas JM, Levy RB, Mahadomrongkul V, Shirao T, Aoki C, Huerta PT: AMPA receptor downscaling at the onset of Alzheimer's disease pathology in double knock-in mice. Proc Natl Acad Sci USA 2006: 103: 3410-3415.
46. Frost JL, Liu B, Kleinschmidt M, Schilling S, Demuth, H-U, Lemere CA: Passive immunization against pyroglutamate-3 amyloid-β reduces plaque burden in Alzheimer-like transgenic mice: a pilot study. Neurodegener Dis 2012; 10: 265-270.
47. Marcello A, Wirths O, Schneider-Axmann T, Degerman-Gunnarsson M, Lannfelt L, Bayer TA: Reduced levels of IgM autoantibodies against N-truncated pyroglutamate Aβ in plasma of patients with Alzheimer's disease. Neurobiol Aging 2011; 32: 1379-1387.
48. Wirths O, Erck C, Martens H, Harmeier A, Geumann C, Jawhar S, Kumar S, Multhaup G, Walter J, Ingelsson M, Degerman-Gunnarsson M, Kalimo H, Huitinga I, Lannfelt L, Bayer TA: Identification of low molecular weight pyroglutamate Aβ oligomers in Alzheimer disease: a novel tool for therapy and diagnosis. J Biol Chem 2010b;285: 41517-41524.
49. Venkataramani V, Wirths O, Budka H, Härtig W, Kovacs GG, Bayer TA: Antibody 9D5 recognizes oligomeric pyroglutamate Aβ in a fraction of Aβ deposits in Alzheimer disease-no cross-reactivity with other protein aggregates. J Alzheimers Dis 2012; 29: 361-371.