Glutaminyl cyclase in human cortex: Correlation with (pGlu)-amyloid-β load and cognitive decline in Alzheimer's disease

Journal of Alzheimer's Disease

Volumn 39, Issue 2, 2014, Pages 385-400

  Morawski, Markus ^a   Schilling, Stephan ^b   Kreuzberger, Moritz ^a   Waniek, Alexander ^a   Jäger, Carsten ^a   Koch, Birgit ^b   Cynis, Holger ^b,c   Kehlen, Astrid ^b   Arendt, Thomas ^a   Hartlage Rübsamen, Maike ^a   Demuth, Hans Ulrich ^b   Roßnera, Steffen ^a  

^a UNIVERSITY OF LEIPZIG   (Germany)

^b PROBIODRUG AG   (Germany)

^c BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

Alzheimer's disease; entorhinal cortex; glutaminyl cyclase; Mini Mental State Examination; pyroglutamate A

Indexed keywords

AMYLOID BETA PROTEIN; GLUTAMINE; GLUTAMINYLCYCLASE; PYROGLUTAMIC ACID; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ARTICLE; BRAIN REGION; BRAIN TISSUE; COGNITIVE DEFECT; CONTROLLED STUDY; CORRELATION ANALYSIS; ENTORHINAL CORTEX; ENZYME ACTIVITY; HUMAN; IMMUNOHISTOCHEMISTRY; IMMUNOREACTIVITY; MINI MENTAL STATE EXAMINATION; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; STEREOLOGY; TEMPORAL CORTEX;

ALZHEIMER'S DISEASE; ENTORHINAL CORTEX; GLUTAMINYL CYCLASE; MINI-MENTAL STATE EXAMINATION; PYROGLUTAMATE-AΒ;

AGED; AGED, 80 AND OVER; ALZHEIMER DISEASE; AMINOACYLTRANSFERASES; AMYLOID BETA-PEPTIDES; COGNITION DISORDERS; ENTORHINAL CORTEX; FEMALE; HUMANS; MALE; NEURONS; PSYCHIATRIC STATUS RATING SCALES; PYRROLIDONECARBOXYLIC ACID; RNA, MESSENGER; TEMPORAL LOBE;

EID: 84893929085     PISSN: 13872877     EISSN: 18758908     Source Type: Journal    
DOI: 10.3233/JAD-131535     Document Type: Article

References (56)

1. 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 (2011) In vivo positron emission tomographic imaging of glial responses to amyloid-beta and tau pathologies in mouse models of Alzheimer's disease and related disorders. J Neurosci 31, 4720-4730.
2. Leung KK, Bartlett JW, Barnes J, Manning EN, Ourselin S, Fox NC; Alzheimer's Disease Neuroimaging Initiative (2013) Cerebral atrophy in mild cognitive impairment and Alzheimer disease: Rates and acceleration. Neurology 80, 648-654.
3. 11C]PK11195 positron emission tomography study. Neurobiol Aging 34, 128-136.
4. Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 81, 239-259.
5. Mirra SS, Heyman A,McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, van Belle G, Berg L (1991) The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology 41, 479-486.
6. Selkoe DJ, Schenk D (2003) Alzheimer's disease: Molecular understanding predicts amyloid based therapeutics. Annu Rev Pharmacol Toxicol 43, 545-584.
7. Haass C (2004) Take five-BACE and the gamma-secretase quartet conduct Alzheimer's amyloid beta-peptide generation. EMBO J 23, 483-488.
8. Saido TC, Iwatsubo T, Mann DM, Shimada H, Ihara Y, Kawashima S (1995) Dominant and differential deposition of distinct beta-amyloid peptide species, Abeta N3(pE), in senile plaques. Neuron 14, 457-466.
9. Saido TC, Yamao H, Iwatsubo T, Kawashima S (1996) Amino-and carboxyl-terminal heterogeneity of beta-amyloid peptides deposited in human brain. Neurosci Lett 215, 173-176.
10. Russo C, Schettini G, Saido TC, Hulette C, Lippa C, Lannfelt L, Ghetti B, Gambetti P, Tabaton M, Teller JK (2000) Presenilin-1 mutations in Alzheimer's disease. Nature 405, 531-532.
11. Sevalle J, Amoyel A, Robert P, Fournié-Zaluski MC, Roques B, Checler F (2009) Aminopeptidase A contributes to the N-terminal truncation of amyloid beta-peptide. J Neurochem 109, 248-256.
12. Miravalle L, Calero M, Takao M, Roher AE, Ghetti B, Vidal R (2005) Amino-terminally truncated Abeta peptide species are the main component of cottonwool plaques. Biochemistry 44, 10810-10821.
13. 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 (2005) Beta-amyloid is different in normal aging and in Alzheimer's disease. J Biol Chem 280, 34186-34192.
14. Portelius E, Bogdanovic N, Gustavsson MK, Volkmann I, Brinkmalm G, Zetterberg H, Winblad B, Blennow K (2010) Mass spectrometric characterization of brain amyloid beta isoform signatures in familial and sporadic Alzheimer's disease. Acta Neuropathol 120, 185-193.
15. HeW, Barrow CJ (1999) The A beta 3-pyroglutamyl and 11-pyroglutamyl peptides found in senile plaque have greater beta-sheet forming and aggregation propensities in vitro than full-length A beta. Biochemistry 38, 10871-10877.
16. Russo C, Violani E, Salis S, Venezia V, Dolcini V, Damonte G, Benatti U, D'Arrigo C, Patrone E, Carlo P, Schettini G (2002) Pyroglutamate-modified amyloid beta-peptides-AbetaN3(pE)-strongly affect cultured neuron and astrocyte survival. J Neurochem 82, 1480-1489.
17. Schilling S, LauberT, Schaupp M, Manhart S, Scheel E,Böhm G, Demuth HU (2006) On the seeding and oligomerization of pGlu-amyloid peptides (in vitro). Biochemistry 45, 12393-12399.
18. Schlenzig D, Manhart S, Cinar Y, Kleinschmidt M, Hause G, Willbold D, Funke SA, Schilling S, Demuth HU (2009) Pyroglutamate formation influences solubility and amyloidogenicity of amyloid peptides. Biochemistry 48, 7072-7078.
19. D'Arrigo C, Tabaton M, Perico A (2009) N-terminal truncated pyroglutamyl beta amyloid peptide Abetapy3-42 shows a faster aggregation kinetics than the full-length Abeta1-42. Biopolymers 91, 861-873.
20. McColl G, Roberts BR, Gunn AP, Perez KA, Tew DJ, Masters CL, Barnham KJ, Cherny RA, Bush AI (2009) The Caenorhabditis elegansAβ1-42 model of Alzheimer's disease predominantly expresses Aβ3-42. J Biol Chem 284, 22697-22702.
21. SaidoTC(1998) Alzheimer's disease as proteolytic disorders: Anabolism and catabolism of beta-amyloid. Neurobiol Aging 19, S69-S75.
22. Acero G, Manutcharian K, Vasilevko V, Munguia ME, Govezensky T, Coronas G, Luz-Madrigal A, Cribbs DH, Gevorkian G (2009) Immunodominant epitope and properties of pyroglutamate-modified Aβ-specific antibodies produced in rabbits. J Neuroimmunol 213, 39-46.
23. Wirths O, Breyhan H, Cynis H, Schilling S, Demuth HU, Bayer TA (2009) Intraneuronal pyroglutamate-Abeta 3-42 triggers neurodegeneration and lethal neurological deficits in a transgenic mouse model. Acta Neuropathol 118, 487-496.
24. Nussbaum JM, Schilling S, Cynis H, Silva A, Swanson E, Wangsanut T, Tayler K, Wiltgen B, Hatami A, Rönicke R, Reymann K, Hutter-Paier B, Alexandru A, Jagla W, Graubner S, Glabe CG, Demuth HU, Bloom GS (2012) Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-β. Nature 485, 651-655.
25. Maeda J, Ji B, Irie T, Tomiyama T, Maruyama M, Okauchi T, Staufenbiel M, Iwata N, Ono M, Saido TC, Suzuki K, Mori H, Higuchi M, Suhara T (2007) Longitudinal, quantitative assessment of amyloid, neuroinflammation, and anti-amyloid treatment in a living mouse model of Alzheimer's disease enabled by positron emission tomography. J Neurosci 27, 10957-10968.
26. Schilling S, Hoffmann T, Manhart S, Hoffmann M, Demuth HU (2004) Glutaminyl cyclases unfold glutamyl cyclase activity under mild acid conditions. FEBS Lett 563, 191-196.
27. Cynis H, Schilling S, Bodnar M, Hoffmann T, Heiser U, Saido TC, DemuthHU(2006) Inhibition of glutaminyl cyclase alters pyroglutamate formation in mammalian cells. Biochim Biophys Acta 1764, 1618-1625.
28. Cynis H, Scheel E, Saido TC, Schilling S, Demuth HU (2008) Amyloidogenic processing of amyloid precursor protein: Evidence of a pivotal role of glutaminyl cyclase in generation of pyroglutamate-modified amyloid-beta. Biochemistry 47, 7405-7413.
29. 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 (2008) Glutaminyl cyclase inhibition attenuates pyroglutamate Abeta and Alzheimer's disease-like pathology. Nature Med 14, 1106-1111.
30. Schilling S, Appl T, Hoffmann T, Cynis H, Schulz K, JaglaW, Friedrich D,Wermann M, Buchholz M, Heiser U, vonHörsten S, Demuth HU (2008) Inhibition of glutaminyl cyclase prevents pGlu-Aβ formation after intracortical/hippocampal microinjection in vivo/in situ. J Neurochem 106, 1225-1236.
31. Fischer WH, Spiess J (1987) Identification of a mammalian glutaminyl cyclase converting glutaminyl into pyroglutamyl peptides. Proc Natl Acad Sci U S A 84, 3628-3632.
32. Busby WH, Quackenbush GE, Humm J, Youngblood WW, Kizer JS (1987) An enzyme(s) that converts glutaminylpeptides into pyroglutamyl-peptides. J Biol Chem 262, 8532-8536.
33. Pohl T, Zimmer M, Mugele K, Spiess J (1991) Primary structure and functional expression of a glutaminyl cyclase. Proc Natl Acad Sci U S A 88, 10059-10063.
34. Böckers TM, Kreutz MR, Pohl T (1995) Glutaminyl-cyclase expression in the bovine/porcine hypothalamus and pituitary. J Neuroendocrinol 7, 445-453.
35. Morawski M, Hartlage-Rübsamen M, Jäger C, Waniek A, Schilling S, Schwab C, McGeer P, Arendt T, Demuth HU, Roßner S (2010) Distinct glutaminyl cyclase expression in Edinger-Westphal nucleus, locus coeruleus and nucleus basalis Meynert contributes to pGlu-Aβ pathology in Alzheimer's disease. Acta Neuropathol 120, 195-207.
36. Hartlage-Rübsamen M, Staffa K, Waniek A, Wermann M, Hoffmann T, Cynis H, Schilling S, Demuth HU, Roßner S (2009)Developmental expression and subcellular localization of glutaminyl cyclase in mouse brain. Int J Dev Neurosci 27, 825-835.
37. Hartlage-Rübsamen M, Morawski M, Waniek A, Jäger C, Zeitschel U, Koch B, Cynis H, Schilling S, Schliebs R, Demuth HU, Roßner S (2011) Glutaminyl cyclase contributes to the formation of focal and diffuse pyroglutamate (pGlu)-Aβ deposits in hippocampus via distinct cellular mechanisms. Acta Neuropathol 121, 705-719.
38. 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 (2011) Selective hippocampal neurodegeneration in transgenic mice expressing small amounts of truncated Aβis induced by pyroglutamate-Aβformation. J Neurosci 31, 12790-12801.
39. Jawhar S, Wirths O, Schilling S, Graubner S, Demuth HU, Bayer TA (2011) Overexpression of glutaminyl cyclase, the enzyme responsible for pyroglutamate Abeta formation, induces behavioral deficits, and glutaminyl cyclase knockout rescues the behavioral phenotype in 5XFAD mice. J Biol Chem 286, 4454-4460.
40. Beach TG, Sue LI,Walker DG, Roher AE, Lue L, Vedders L, Connor DJ, Sabbagh MN, Rogers J (2008) The Sun Health Research Institute Brain Donation Program: Description and experience, 1987-2007. Cell Tissue Bank 9, 229-245.
41. Mai JK, Assheuer J, Paxinos G (2004) Atlas of the human brain. Academic Press, San Diego.
42. 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 (2010) Pyroglutamate Abeta pathology in APP/PS1KI mice, sporadic and familial Alzheimer's disease cases. J Neural Transm 117, 85-96.
43. KonigsmarkBW(1970) Methods for the counting of neurons. In Contemporary Research Methods in Neuroanatomy, Nauta WHJ, Ebbesson SOE, eds. Springer, Berlin, pp. 315-380.
44. Andersen CL, Ledet-Jensen J, Ørntoft T (2004) Normalization of real-time quantitative RT-PCR data: A model based variance estimation approach to identify genes suited for normalization-applied to bladder-and colon-cancer data-sets. Cancer Res 64, 5245-5250.
45. 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 (2010) Identification of low molecular weight pyroglutamate Abeta oligomers in Alzheimer disease:Anovel tool for therapy and diagnosis. J Biol Chem 285, 41517-41524.
46. Frost JL, Liu B, Kleinschmidt M, Schilling S, Demuth HU, Lemere CA (2012) Passive immunization against pyroglutamate-3 amyloid-β reduces plaque burden in Alzheimer-like transgenic mice: A pilot study. Neurodegener Dis 10, 265-270.
47. Demattos RB, Lu J, Tang Y, RackeMM, Delong CA, Tzaferis JA, Hole JT, Forster BM, McDonnell PC, Liu F, Kinley RD, Jordan WH, Hutton ML (2012) A plaque-specific antibody clears existing β-amyloid plaques in Alzheimer's disease mice. Neuron 76, 908-920.
48. Weber F, Lues I, Meyer A, Hoffmann T, Pokorny R, Lopez L, Demuth HU, Glund K (2013) A phase 1 study assessing safety, pharmacokinetics and pharmacodynamics of PQ912, the first glutaminyl cyclase (QC) inhibitor to treat AD. 11th Conference on Alzheimer's disease and Parkinson's disease. Florence, March 6-10, 2013; Abstract 1453.
49. Saygin AP, Dick F,Wilson SM, Dronkers NF, Bates E (2003) Neural resources for processing language and environmental sounds: Evidence from aphasia. Brain 126, 928-945.
50. Jacobs J, Kahana MJ, Ekstrom AD, Mollison MV, Fried I (2010) A sense of direction in human entorhinal cortex. Proc Natl Acad Sci U S A 107, 6487-6492.
51. Suthana N, Haneef Z, Stern J, Mukamel R, Behnke E, Knowlton B, Fried I (2012) Memory enhancement and deep-brain stimulation of the entorhinal Area. N Engl J Med 366, 501-510.
52. Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT (2011) Neuropathological alterations in Alzheimer's disease. Cold Spring Harb Perspect Med 1, a006189.
53. De Kimpe L, Bennis A, Zwart R, van Haastert ES, Hoozemans JJ, Scheper W (2012) Disturbed Ca2+ homeostasis increases glutaminyl cyclase expression; connecting two early pathogenic events in Alzheimer's disease in vitro. PLOS One 7, e44674.
54. ValentiMT, Bolognin S, Zanatta C, Donatelli L, Innamorati G, Pampanin M, Zanusso G, Zatta P, Dalle Carbonare L (2013) Increased glutaminyl cyclase expression in peripheral blood of Alzheimer's disease patients. J Alzheimers Dis 34, 263-271.
55. Muresan Z, Muresan V (2008) Seeding neuritic plaques from the distance: A possible role for brainstem neurons in the development of Alzheimer's disease. Neurodegener Dis 5, 250-253.
56. Christensen DZ, Kraus SL, Flohr A, Cotel MC, Wirths O, BayerTA(2008)Transient intraneuronalAβrather than extracellular plaque pathology correlates with neuron loss in the frontal cortex of APP/PS1 mice. Acta Neuropathol 116, 647-655