Klafki, Hans-Wolfgang

[["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Pharmacopsychiatry"],["dc.bibliographiccitation.volume","38"],["dc.contributor.author","Maler, Juan Manuel"],["dc.contributor.author","Esselmann, Herrmann"],["dc.contributor.author","Dyrks, T."],["dc.contributor.author","Klafki, H."],["dc.contributor.author","Fiszer, M."],["dc.contributor.author","Paul, S."],["dc.contributor.author","Reulbach, Udo"],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Ruther, Eckart"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Wiltfang, J."],["dc.date.accessioned","2018-11-07T10:56:36Z"],["dc.date.available","2018-11-07T10:56:36Z"],["dc.date.issued","2005"],["dc.format.extent","262"],["dc.identifier.isi","000232591900164"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50051"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Georg Thieme Verlag Kg"],["dc.publisher.place","Stuttgart"],["dc.relation.conference","24th Symposium of the Arbeitsgemeinschaft-fur-Neuropsychopharmakologie-und-Pharmakopsychiatrie (AGNP)"],["dc.relation.eventlocation","Munich, GERMANY"],["dc.relation.issn","0176-3679"],["dc.title","Specific inhibition of beta-amyloid peptide secretion by ZK808762 mimicks the effect of non-steroidal antiinflammatory drugs"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","203"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Neural Transmission"],["dc.bibliographiccitation.lastpage","212"],["dc.bibliographiccitation.volume","116"],["dc.contributor.author","Welge, Volker"],["dc.contributor.author","Fiege, Oliver"],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Esselmann, Hermann"],["dc.contributor.author","Klafki, Hans-Wolfgang"],["dc.contributor.author","Wolf, Stefanie"],["dc.contributor.author","Trenkwalder, Claudia"],["dc.contributor.author","Otto, Markus"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Bibl, Mirko"],["dc.date.accessioned","2018-11-07T08:33:10Z"],["dc.date.available","2018-11-07T08:33:10Z"],["dc.date.issued","2009"],["dc.description.abstract","Cerebrospinal fluid (CSF) concentrations of amyloid-beta (A beta) 1-38, 1-40, 1-42, total-tau and phospho-tau in samples from 156 patients with Alzheimer's disease (AD) (n = 44), depressive cognitive complainers (DCC, n = 25) and various other forms of non-Alzheimer dementias (NAD, n = 87) were analyzed by electrochemiluminescence and enzyme linked immunosorbent assay, respectively. A significant decrease of CSF A beta 1-42 was the most powerful single marker for differentiation of AD from DCC, yielding accuracies of beyond 85%. Increased p-tau and the ratio A beta 1-42/A beta 1-38 yielded accuracies of beyond 80 and 85%, respectively, to discriminate AD versus NAD. Combining p-tau with A beta 1-42/A beta 1-38 resulted in a sensitivity of 94% for detection of AD and 85% specificity for excluding NAD. Decreased CSF A beta 1-42 represents a core biomarker for AD. The lack of specificity for exclusion of NAD can be most effectively compensated by the ratio A beta 1-42/A beta 1-38. The ratio A beta 1-42/A beta 1-38/p-tau powerfully discriminates AD versus NAD and fulfils the accuracy requirements for an applicable screening and differential diagnostic AD biomarker."],["dc.identifier.doi","10.1007/s00702-008-0177-6"],["dc.identifier.isi","000269823900011"],["dc.identifier.pmid","19142572"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17511"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Wien"],["dc.relation.issn","0300-9564"],["dc.title","Combined CSF tau, p-tau181 and amyloid-beta 38/40/42 for diagnosing Alzheimer's disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1177"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","1187"],["dc.bibliographiccitation.volume","129"],["dc.contributor.author","Bibl, Mirko"],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Esselmann, Herrmann"],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Klafki, H. W."],["dc.contributor.author","Sparbier, Katrin"],["dc.contributor.author","Smirnov, Alexey"],["dc.contributor.author","Cepek, L."],["dc.contributor.author","Trenkwalder, Claudia"],["dc.contributor.author","Ruther, Eckart"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Otto, Markus"],["dc.contributor.author","Wiltfang, J."],["dc.date.accessioned","2018-11-07T09:51:06Z"],["dc.date.available","2018-11-07T09:51:06Z"],["dc.date.issued","2006"],["dc.description.abstract","As the differential diagnosis of dementias based on established clinical criteria is often difficult, biomarkers for applicable diagnostic testing are currently under intensive investigation. Amyloid plaques deposited in the brain of patients suffering from Alzheimer's disease, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) mainly consist of carboxy-terminally elongated forms of amyloid-beta (A beta) peptides, such as A beta 1-42. Absolute A beta 1-42 levels in CSF have shown diagnostic value for the diagnosis of Alzheimer's disease, but the discrimination among Alzheimer's disease, DLB and PDD was poor. A recently established quantitative urea-based A beta-sodium-dodecylsulphate-polyacrylamide-gel-electrophoresis with Western immunoblot (A beta-SDS-PAGE/immunoblot) revealed a highly conserved A beta peptide pattern of the carboxy-terminally truncated A beta peptides 1-37, 1-38, 1-39 in addition to 1-40 and 1-42 in human CSF. We used the A beta-SDS-PAGE/immunoblot to investigate the CSF of 23 patients with Alzheimer's disease, 21 with DLB, 21 with PDD and 23 non-demented disease controls (NDC) for disease-specific alterations of the A beta peptide patterns in its absolute and relative quantities. The diagnostic groups were matched for age and severity of dementia. The present study is the first attempt to evaluate the meaning of A beta peptide patterns in CSF for differential diagnosis of the three neurodegenerative diseases-Alzheimer's disease, DLB and PDD. The A beta peptide patterns displayed disease-specific variations and the ratio of the differentially altered A beta 1-42 to the A beta 1-37 levels subsequently discriminated all diagnostic groups from each other at a highly significant level, except DLB from PDD. Additionally, a novel peptide with A beta-like immunoreactivity was observed constantly in the CSF of all 88 investigated patients. The pronounced percentage increase of this peptide in DLB allowed a highly significant discrimination from PDD. Using a cut-off point of 0.954%, this marker yielded a diagnostic sensitivity and specificity of 81 and 71%, respectively. From several lines of indication, we consider this peptide to represent an oxidized alpha-helical form of A beta 1-40 (A beta 1-40( )). The increased abundance of A beta 1-40( ) probably reflects a disease-specific alteration of the A beta 1-40 metabolism in DLB. We conclude that A beta peptide patterns reflect disease-specific pathophysiological pathways of different dementia syndromes as distinct neurochemical phenotypes. Although A beta peptide patterns failed to fulfil the requirements for a sole biomarker, their combined evaluation with other biomarkers is promising in neurochemical dementia diagnosis. It is noteworthy that DLB and PDD exhibit distinct clinical temporal courses, despite their similar neuropathological appearance. Their distinct molecular phenotypes support the view of different pathophysiological pathways for each of these neurodegenerative diseases."],["dc.identifier.doi","10.1093/brain/awl063"],["dc.identifier.isi","000236998000012"],["dc.identifier.pmid","16600985"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35846"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0006-8950"],["dc.title","CSF amyloid-beta-peptides in Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease dementia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Neurobiology of Aging"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Wiltfang, J."],["dc.contributor.author","Esselmann, Herrmann"],["dc.contributor.author","Bibl, Mirko"],["dc.contributor.author","Smirnov, Alexey"],["dc.contributor.author","Paul, S."],["dc.contributor.author","Ruether, Eckhart"],["dc.contributor.author","Otto, Markus"],["dc.contributor.author","Schmidt, B."],["dc.contributor.author","Klafki, H. W."],["dc.contributor.author","Maler, M."],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Dyrks, T."],["dc.contributor.author","Bienert, M."],["dc.contributor.author","Beyermann, M."],["dc.date.accessioned","2018-11-07T10:23:20Z"],["dc.date.available","2018-11-07T10:23:20Z"],["dc.date.issued","2002"],["dc.format.extent","S275"],["dc.identifier.isi","000177465301009"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42438"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.publisher.place","New york"],["dc.relation.issn","0197-4580"],["dc.title","Highly conserved and disease-specific patterns of carboxyterminally truncated abeta peptides 1-37/38/39 in addition to 1-40/42 in Alzheimer's disease and in patients with chronic neuroinflammation"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","613"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Alzheimer s Disease"],["dc.bibliographiccitation.lastpage","622"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Klafki, Hans-Wolfgang"],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Kamrowski-Kruck, Heike"],["dc.contributor.author","Maler, Juan Manuel"],["dc.contributor.author","Mueller, Katharina"],["dc.contributor.author","Peters, Oliver"],["dc.contributor.author","Heuser, Isabella"],["dc.contributor.author","Jessen, Frank"],["dc.contributor.author","Popp, Julius"],["dc.contributor.author","Froelich, Lutz"],["dc.contributor.author","Wolf, Stefanie"],["dc.contributor.author","Prinz, Berit"],["dc.contributor.author","Luckhaus, Christian"],["dc.contributor.author","Schroeder, Johannes"],["dc.contributor.author","Pantel, Johannes"],["dc.contributor.author","Gertz, Hermann-Josef"],["dc.contributor.author","Koelsch, Heike"],["dc.contributor.author","Mueller, Bernhard W."],["dc.contributor.author","Esselmann, Hermann"],["dc.contributor.author","Bibl, Mirko"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Wiltfang, Jens"],["dc.date.accessioned","2018-11-07T08:34:46Z"],["dc.date.available","2018-11-07T08:34:46Z"],["dc.date.issued","2009"],["dc.description.abstract","The clinical diagnosis of neurodegenerative disorders can be supported by soluble biomarkers in cerebrospinal fluid (CSF), such as tau protein, phospho-tau, and amyloid-beta peptides. In particular, increased CSF levels of phospho-tau in Alzheimer's disease appear to reflect disease specific pathological processes. We report here evidence for the presence of soluble MAP-kinase ERK1/2 in a small set of human CSF samples from patients with Alzheimer's disease, frontotemporal degeneration, and mild cognitive impairment. The level of total ERK1/2 in CSF as measured by electrochemiluminescent assay was correlated with that of total tau and phospho-tau. A small fraction of ERK1/2 in a pooled CSF sample was found to be in the doubly phosphorylated (activated) state. Our findings suggest that i) MAP kinase ERK1/2 is apparently released under neurodegenerative conditions in parallel with tau and phospho-tau and ii) in the future, it might be possible to find in CSF samples evidence for disease related alterations in brain kinase signaling pathways by use of highly sensitive and activation-state specific anti-kinase antibodies."],["dc.identifier.doi","10.3233/JAD-2009-1167"],["dc.identifier.isi","000272860100013"],["dc.identifier.pmid","19625747"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17898"],["dc.notes.claim","Wed Nov 07 12:36:41 UTC 2018:dc_contributor_author:Hallo Sabine, das ist nicht mein Artikel.... :-)"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Ios Press"],["dc.relation.issn","1387-2877"],["dc.title","Measurement of ERK 1/2 in CSF from Patients with Neuropsychiatric Disorders and Evidence for the Presence of the Activated Form"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","481"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","496"],["dc.bibliographiccitation.volume","81"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Esselmann, Hermann"],["dc.contributor.author","Bibl, M."],["dc.contributor.author","Smirnov, A."],["dc.contributor.author","Otto, Markus"],["dc.contributor.author","Paul, S."],["dc.contributor.author","Schmidt, B."],["dc.contributor.author","Klafki, Hans-Wolfgang"],["dc.contributor.author","Maler, Manuel"],["dc.contributor.author","Dyrks, T."],["dc.contributor.author","Bienert, M."],["dc.contributor.author","Beyermann, Michael"],["dc.contributor.author","Rüther, Eckart"],["dc.contributor.author","Kornhuber, Johannes"],["dc.date.accessioned","2017-09-07T11:44:26Z"],["dc.date.available","2017-09-07T11:44:26Z"],["dc.date.issued","2003"],["dc.description.abstract","Human lumbar CSF patterns of Aβ peptides were analysed by urea-based β-amyloid sodium dodecyl sulphate polyacrylamide gel electrophoresis with western immunoblot (Aβ-SDS–PAGE/immunoblot). A highly conserved pattern of carboxyterminally truncated Aβ1–37/38/39 was found in addition to Aβ1–40 and Aβ1–42. Remarkably, Aβ1–38 was present at a higher concentration than Aβ1–42, being the second prominent Aβ peptide species in CSF. Patients with Alzheimer's disease (AD, n = 12) and patients with chronic inflammatory CNS disease (CID, n = 10) were differentiated by unique CSF Aβ peptide patterns from patients with other neuropsychiatric diseases (OND, n = 37). This became evident only when we investigated the amount of Aβ peptides relative to their total Aβ peptide concentration (Aβ1–x%, fractional Aβ peptide pattern), which may reflect disease-specific γ-secretase activities. Remarkably, patients with AD and CID shared elevated Aβ1–38% values, whereas otherwise the patterns were distinct, allowing separation of AD from CID or OND patients without overlap. The presence of one or two ApoE ε4 alleles resulted in an overall reduction of CSF Aβ peptides, which was pronounced for Aβ1–42. The severity of dementia was significantly correlated to the fractional Aβ peptide pattern but not to the absolute Aβ peptide concentrations."],["dc.identifier.doi","10.1046/j.1471-4159.2002.00818.x"],["dc.identifier.gro","3151651"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8468"],["dc.language.iso","en"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","chake"],["dc.relation.issn","0022-3042"],["dc.title","Highly conserved and disease-specific patterns of carboxyterminally truncated Aβ peptides 1-37/38/39 in addition to 1-40/42 in Alzheimer's disease and in patients with chronic neuroinflammation"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","24"],["dc.bibliographiccitation.journal","Neurobiology of Disease"],["dc.bibliographiccitation.lastpage","35"],["dc.bibliographiccitation.volume","73"],["dc.contributor.author","Oberstein, Timo Jan"],["dc.contributor.author","Spitzer, Philipp"],["dc.contributor.author","Klafki, Hans-Wolfgang"],["dc.contributor.author","Linning, Philipp"],["dc.contributor.author","Neff, Florian"],["dc.contributor.author","Knölker, Hans-Joachim"],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Maler, Juan Manuel"],["dc.date.accessioned","2017-09-07T11:44:32Z"],["dc.date.available","2017-09-07T11:44:32Z"],["dc.date.issued","2014"],["dc.description.abstract","The neuropathological hallmarks of Alzheimer's disease include extracellular neuritic plaques and neurofibrillary tangles. The neuritic plaques contain β-amyloid peptides (Aβ peptides) as the major proteinaceous constituent and are surrounded by activated microglia and astrocytes as well as dystrophic neurites. N-terminally truncated forms of Aβ peptides are highly prevalent in neuritic plaques, including Aβ 3-x beginning at Glu eventually modified to pyroglutamate (Aβ N3pE-x), Aβ 2-x, Aβ 4-x, and Aβ 5-x. The precise origin of the different N-terminally modified Aβ peptides currently remains unknown. To assess the contribution of specific cell types to the formation of different N-terminally truncated Aβ peptides, supernatants from serum-free primary cell cultures of chicken neurons, astrocytes, and microglia, as well as human astrocytes, were analyzed by Aβ-ELISA and one- and two-dimensional SDS-urea polyacrylamide gel electrophoresis followed by immunoblot analysis. To evaluate the contribution of β- and γ-secretase to the generation of N-terminally modified Aβ, cultured astrocytes were treated with membrane-anchored “tripartite β-secretase (BACE1) inhibitors” and the γ-secretase inhibitor DAPT. Neurons, astrocytes, and microglia each exhibited cell type-specific patterns of secreted Aβ peptides. Neurons predominantly secreted Aβ peptides that begin at Asp1, whereas those released from astrocytes and microglia included high proportions of N-terminally modified Aβ peptides, presumably including Aβ 2/3-x and 4/5-x. The inhibition of BACE1 reduced the amount of Aβ 1-x in cell culture supernatants but not the amount of Aβ 2-x."],["dc.identifier.doi","10.1016/j.nbd.2014.08.031"],["dc.identifier.gro","3151693"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11345"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8512"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","public"],["dc.notes.submitter","chake"],["dc.relation.issn","0969-9961"],["dc.rights","CC BY-NC-SA 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-sa/3.0"],["dc.title","Astrocytes and microglia but not neurons preferentially generate N-terminally truncated Aβ peptides"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","PROTEOMICS - CLINICAL APPLICATIONS"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Bibl, Mirko"],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Esselmann, Hermann"],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Klafki, Hans-Wolfgang"],["dc.contributor.author","Welge, Volker"],["dc.contributor.author","Wolf, Stefanie"],["dc.contributor.author","Trenkwalder, Claudia"],["dc.contributor.author","Otto, Markus"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Wiltfang, Jens"],["dc.date.accessioned","2018-11-07T08:29:36Z"],["dc.date.available","2018-11-07T08:29:36Z"],["dc.date.issued","2009"],["dc.format.extent","754"],["dc.identifier.isi","000267915300011"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16692"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-v C H Verlag Gmbh"],["dc.relation.issn","1862-8346"],["dc.title","CSF amyloid-beta 1-38 and 1-42 in FTD and AD: Biomarker performance critically depends on the detergent accessible fraction (vol 2, pg 1548, 2008)"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Molecular Neuroscience"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Oberstein, Timo Jan"],["dc.contributor.author","Utz, Janine"],["dc.contributor.author","Spitzer, Philipp"],["dc.contributor.author","Klafki, Hans Wolfgang"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Maler, Juan Manuel"],["dc.date.accessioned","2021-04-14T08:29:50Z"],["dc.date.available","2021-04-14T08:29:50Z"],["dc.date.issued","2021"],["dc.description.abstract","Astrocytes may not only be involved in the clearance of Amyloid beta peptides (Aβ) in Alzheimer's disease (AD), but appear to produce N-terminally truncated Aβ (Aβn−x) independently of BACE1, which generates the N-Terminus of Aβ starting with Asp1 (Aβ1−x). A candidate protease for the generation of Aβn−x is cathepsin B (CatB), especially since CatB has also been reported to degrade Aβ, which could explain the opposite roles of astrocytes in AD. In this study, we investigated the influence of CatB inhibitors and the deletion of the gene encoding CatB (CTSB) using CRISPR/Cas9 technology on Aβ2−x and Aβ1−x levels in cell culture supernatants by one- and two-dimensional Urea-SDS-PAGE followed by immunoblot. While the cell-permeant inhibitors E64d and CA-074 Me did not significantly affect the Aβ1−x levels in supernatants of cultured chicken and human astrocytes, they did reduce the Aβ2−x levels. In the glioma-derived cell line H4, the Aβ2−x levels were likewise decreased in supernatants by treatment with the more specific, but cell-impermeant CatB-inhibitor CA-074, by CA-074 Me treatment, and by CTSB gene deletion. Additionally, a more than 2-fold increase in secreted Aβ1−x was observed under the latter two conditions. The CA-074 Me-mediated increase of Aβ1−x, but not the decrease of Aβ2−x, was influenced by concomitant treatment with the vacuolar H+-ATPase inhibitor Bafilomycin A1. This indicated that non-lysosomal CatB mediated the production of Aβ2−x in astrocytes, while the degradation of Aβ1−x seemed to be dependent on lysosomal CatB in H4 cells, but not in primary astrocytes. These findings highlight the importance of considering organelle targeting in drug development to promote Aβ degradation."],["dc.identifier.doi","10.3389/fnmol.2020.615740"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83001"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1662-5099"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.title","The Role of Cathepsin B in the Degradation of Aβ and in the Production of Aβ Peptides Starting With Ala2 in Cultured Astrocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1548"],["dc.bibliographiccitation.issue","10-11"],["dc.bibliographiccitation.journal","PROTEOMICS - CLINICAL APPLICATIONS"],["dc.bibliographiccitation.lastpage","1556"],["dc.bibliographiccitation.volume","2"],["dc.contributor.author","Bibl, Mirko"],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Esselmann, Hermann"],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Klafki, Hans-Wolfgang"],["dc.contributor.author","Welge, Volker"],["dc.contributor.author","Wolf, Stefanie"],["dc.contributor.author","Trenkwalder, Claudia"],["dc.contributor.author","Otto, Markus"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Wiltfang, Jens"],["dc.date.accessioned","2018-11-07T11:10:49Z"],["dc.date.available","2018-11-07T11:10:49Z"],["dc.date.issued","2008"],["dc.description.abstract","Cerebrospinal fluid (CSF) A beta I-38, A beta 1-40, and A beta 1-42 were comparatively analyzed by amyloid-beta SDS-PAGE with Western immunoblot (A beta-SDS-PAGE/immunoblot), electrochemiluminescence detection and ELISA (MSD/ELISA) in patients with Alzheimer's disease (AD, n = 40), frontotemporal dementia (FTD, n = 30), and other dementias (n = 50) and nondemented disease controls (n = 30). CSF A beta-peptide concentrations were higher and selective decreases of CSF A beta 1-38 in FTD and A beta 1-42 in AD were more evident as measured after SDS-denaturizing of samples by A beta-SDS-PAGE/immunoblot. The SDS-accessible pool of CSF A beta 1-38 and A beta 1-42, represented by the individual gain of A beta-peptide yield using A beta-SDS-PAGE/immunoblot, was reduced in both FTD and AD. Accordingly, biomarker accuracies of A beta 1-38 and A beta 1-42 for detection of FTD and AD, respectively declined as determined by MSD/ELISA. We conclude that a pool of CSF A beta 1-38 and A beta 1-42, which shows disease-specific reductions in FTD and AD, may be bound to carriers and can be released by SDS. Assessing this SDS-accessible A beta-peptide pool may crucially enhance the accuracy of CSF biomarker tests. Identifying disease-specific binding properties of affected A beta carriers may elucidate pathogenic aspects and open up a novel field for therapeutic approaches."],["dc.identifier.doi","10.1002/prca.200800006"],["dc.identifier.isi","000260209000017"],["dc.identifier.pmid","21136802"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53291"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-v C H Verlag Gmbh"],["dc.relation.issn","1862-8346"],["dc.title","CSF amyloid-beta 1-38 and 1-42 in FTD and AD: Biomarker performance critically depends on the detergent accessible fraction"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]