{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T20:51:36Z","timestamp":1789159896431,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T00:00:00Z","timestamp":1523923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Oligomeric assemblies of neurotoxic amyloid beta (Abeta) peptides generated by proteolytical processing of the amyloid precursor protein (APP) play a key role in the pathogenesis of Alzheimer\u2019s disease (AD). In recent years, a substantial heterogeneity of Abeta peptides with distinct biophysical and cell biological properties has been demonstrated. Among these, a particularly neurotoxic and disease-specific Abeta variant is N-terminally truncated and modified to pyroglutamate (pE-Abeta). Cell biological and animal experimental studies imply the catalysis of this modification by the enzyme glutaminyl cyclase (QC). However, direct histopathological evidence in transgenic animals from comparative brain region and cell type-specific expression of transgenic hAPP and QC, on the one hand, and on the formation of pE-Abeta aggregates, on the other, is lacking. Here, using single light microscopic, as well as triple immunofluorescent, labeling, we report the deposition of pE-Abeta only in the brain regions of APP-transgenic Tg2576 mice with detectable human APP and endogenous QC expression, such as the hippocampus, piriform cortex, and amygdala. Brain regions showing human APP expression without the concomitant presence of QC (the anterodorsal thalamic nucleus and perifornical nucleus) do not display pE-Abeta plaque formation. However, we also identified brain regions with substantial expression of human APP and QC in the absence of pE-Abeta deposition (the Edinger-Westphal nucleus and locus coeruleus). In these brain regions, the enzymes required to generate N-truncated Abeta peptides as substrates for QC might be lacking. Our observations provide additional evidence for an involvement of QC in AD pathogenesis via QC-catalyzed pE-Abeta formation.<\/jats:p>","DOI":"10.3390\/molecules23040924","type":"journal-article","created":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T03:51:13Z","timestamp":1524023473000},"page":"924","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Immunohistochemical Evidence from APP-Transgenic Mice for Glutaminyl Cyclase as Drug Target to Diminish pE-Abeta Formation"],"prefix":"10.3390","volume":"23","author":[{"given":"Maike","family":"Hartlage-R\u00fcbsamen","sequence":"first","affiliation":[{"name":"Paul Flechsig Institute for Brain Research, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Bluhm","sequence":"additional","affiliation":[{"name":"Paul Flechsig Institute for Brain Research, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Piechotta","sequence":"additional","affiliation":[{"name":"Department of Molecular Drug Design and Target Validation, Fraunhofer Institute for Cell Therapy and Immunology, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Linnert","sequence":"additional","affiliation":[{"name":"Department of Molecular Drug Design and Target Validation, Fraunhofer Institute for Cell Therapy and Immunology, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens-Ulrich","family":"Rahfeld","sequence":"additional","affiliation":[{"name":"Department of Molecular Drug Design and Target Validation, Fraunhofer Institute for Cell Therapy and Immunology, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3505-6795","authenticated-orcid":false,"given":"Hans-Ulrich","family":"Demuth","sequence":"additional","affiliation":[{"name":"Department of Molecular Drug Design and Target Validation, Fraunhofer Institute for Cell Therapy and Immunology, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Lues","sequence":"additional","affiliation":[{"name":"Probiodrug AG, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peer-Hendrik","family":"Kuhn","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Technical University of Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan F.","family":"Lichtenthaler","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 81377 Munich, Germany"},{"name":"Munich Cluster of Systems Neurology (SyNergy), 81377 Munich, Germany"},{"name":"Neuroproteomics, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany"},{"name":"Institute for Advanced Study, Technical University of Munich, 85748 Garching, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Ro\u00dfner","sequence":"additional","affiliation":[{"name":"Paul Flechsig Institute for Brain Research, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna","family":"H\u00f6fling","sequence":"additional","affiliation":[{"name":"Paul Flechsig Institute for Brain Research, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/alzrt258","article-title":"Truncated and modified amyloid-beta species","volume":"6","author":"Kummer","year":"2014","journal-title":"Alzheimers Res. 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