Bayer, Thomas A.

[["dc.bibliographiccitation.artnumber","e34095"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Grimm, Marc-Oliver"],["dc.contributor.author","Zinser, Eva G."],["dc.contributor.author","Groesgen, Sven"],["dc.contributor.author","Hundsdoerfer, Benjamin"],["dc.contributor.author","Rothhaar, Tatjana L."],["dc.contributor.author","Burg, Verena K."],["dc.contributor.author","Kaestner, Lars"],["dc.contributor.author","Bayer, Thomas A."],["dc.contributor.author","Lipp, Peter"],["dc.contributor.author","Mueller, Ulrike"],["dc.contributor.author","Grimm, Heike S."],["dc.contributor.author","Hartmann, Tobias"],["dc.date.accessioned","2018-11-07T09:12:08Z"],["dc.date.available","2018-11-07T09:12:08Z"],["dc.date.issued","2012"],["dc.description.abstract","Gangliosides are important players for controlling neuronal function and are directly involved in AD pathology. They are among the most potent stimulators of A beta production, are enriched in amyloid plaques and bind amyloid beta (A beta). However, the molecular mechanisms linking gangliosides with AD are unknown. Here we identified the previously unknown function of the amyloid precursor protein (APP), specifically its cleavage products A beta and the APP intracellular domain (AICD), of regulating GD3-synthase (GD3S). Since GD3S is the key enzyme converting a-to b-series gangliosides, it therefore plays a major role in controlling the levels of major brain gangliosides. This regulation occurs by two separate and additive mechanisms. The first mechanism directly targets the enzymatic activity of GD3S: Upon binding of A beta to the ganglioside GM3, the immediate substrate of the GD3S, enzymatic turnover of GM3 by GD3S was strongly reduced. The second mechanism targets GD3S expression. APP cleavage results, in addition to A beta release, in the release of AICD, a known candidate for gene transcriptional regulation. AICD strongly down regulated GD3S transcription and knock-in of an AICD deletion mutant of APP in vivo, or knock-down of Fe65 in neuroblastoma cells, was sufficient to abrogate normal GD3S functionality. Equally, knock-out of the presenilin genes, presenilin 1 and presenilin 2, essential for A beta and AICD production, or of APP itself, increased GD3S activity and expression and consequently resulted in a major shift of a- to b-series gangliosides. In addition to GD3S regulation by APP processing, gangliosides in turn altered APP cleavage. GM3 decreased, whereas the ganglioside GD3, the GD3S product, increased A beta production, resulting in a regulatory feedback cycle, directly linking ganglioside metabolism with APP processing and A beta generation. A central aspect of this homeostatic control is the reduction of GD3S activity via an A beta-GM3 complex and AICD-mediated repression of GD3S transcription."],["dc.identifier.doi","10.1371/journal.pone.0034095"],["dc.identifier.isi","000304489000064"],["dc.identifier.pmid","22470521"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7774"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26881"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Amyloid Precursor Protein (APP) Mediated Regulation of Ganglioside Homeostasis Linking Alzheimer's Disease Pathology with Ganglioside Metabolism"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","26"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Molecular Neurodegeneration"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Ramos-Miguel, Alfredo"],["dc.contributor.author","García-Sevilla, Jesús A."],["dc.contributor.author","Barr, Alasdair M."],["dc.contributor.author","Bayer, Thomas A."],["dc.contributor.author","Falkai, Peter"],["dc.contributor.author","Leurgans, Sue E."],["dc.contributor.author","Schneider, Julie A."],["dc.contributor.author","Bennett, David A."],["dc.contributor.author","Honer, William G."],["dc.contributor.author","García-Fuster, M. J."],["dc.date.accessioned","2019-07-09T11:43:17Z"],["dc.date.available","2019-07-09T11:43:17Z"],["dc.date.issued","2017"],["dc.description.abstract","Abstract Background FADD (Fas-associated death domain) adaptor is a crucial protein involved in the induction of cell death but also mediates non-apoptotic actions via a phosphorylated form (p-Ser194-FADD). This study investigated the possible association of FADD forms with age-related neuropathologies, cognitive function, and the odds of dementia in an elderly community sample. Methods FADD forms were quantified by western blot analysis in dorsolateral prefrontal cortex (DLPFC) samples from a large cohort of participants in a community-based aging study (Memory and Aging Project, MAP), experiencing no-(NCI, n = 51) or mild-(MCI, n = 42) cognitive impairment, or dementia (n = 57). Results Cortical FADD was lower in subjects with dementia and lower FADD was associated with a greater load of amyloid-β pathology, fewer presynaptic terminal markers, poorer cognitive function and increased odds of dementia. Together with the observations of FADD redistribution into tangles and dystrophic neurites within plaques in Alzheimer\\’s disease brains, and its reduction in APP23 mouse cortex, the results suggest this multifunctional protein might participate in the mechanisms linking amyloid and tau pathologies during the course of the illness. Conclusions The present data suggests FADD as a putative biomarker for pathological processes associated with the course of clinical dementia."],["dc.identifier.doi","10.1186/s13024-017-0168-x"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14382"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58852"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","BioMed Central"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Decreased cortical FADD protein is associated with clinical dementia and cognitive decline in an elderly community sample"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","269"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Alzheimer's Disease Reports"],["dc.bibliographiccitation.lastpage","278"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Sichler, Marius E."],["dc.contributor.author","Löw, Maximilian J."],["dc.contributor.author","Schleicher, Eva M."],["dc.contributor.author","Bayer, Thomas A."],["dc.contributor.author","Bouter, Yvonne"],["dc.date.accessioned","2021-06-01T10:48:43Z"],["dc.date.available","2021-06-01T10:48:43Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.3233/ADR-190132"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16704"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86031"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","2542-4823"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.title","Reduced Acoustic Startle Response and Prepulse Inhibition in the Tg4-42 Model of Alzheimer’s Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","555"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","566"],["dc.bibliographiccitation.volume","119"],["dc.contributor.author","Christensen, Ditte Zerlang"],["dc.contributor.author","Schneider-Axmann, Thomas"],["dc.contributor.author","Lucassen, Paul J."],["dc.contributor.author","Bayer, Thomas A."],["dc.contributor.author","Wirths, Oliver"],["dc.date.accessioned","2018-11-07T08:43:18Z"],["dc.date.available","2018-11-07T08:43:18Z"],["dc.date.issued","2010"],["dc.description.abstract","In contrast to extracellular plaque and intracellular tangle pathology, the presence and relevance of intraneuronal A beta in Alzheimer's disease (AD) is still a matter of debate. Human brain tissue offers technical challenges such as post-mortem delay and uneven or prolonged tissue fixation that might affect immunohistochemical staining. In addition, previous studies on intracellular A beta accumulation in human brain often used antibodies targeting the C-terminus of A beta and differed strongly in the pretreatments used. To overcome these inconsistencies, we performed extensive parametrical testing using a highly specific N-terminal A beta antibody detecting the aspartate at position 1, before developing an optimal staining protocol for intraneuronal A beta detection in paraffin-embedded sections from AD patients. To rule out that this antibody also detects the beta-cleaved APP C-terminal fragment (beta-CTF, C99) bearing the same epitope, paraffin-sections of transgenic mice overexpressing the C99-fragment were stained without any evidence for cross-reactivity in our staining protocol. The staining intensity of intraneuronal A beta in cortex and hippocampal tissue of 10 controls and 20 sporadic AD cases was then correlated to patient data including sex, Braak stage, plaque load, and apolipoprotein E (ApoE) genotype. In particular, the presence of one or two ApoE4 alleles strongly correlated with an increased accumulation of intraneuronal A beta peptides. Given that ApoE4 is a major genetic risk factor for AD and is involved in neuronal cholesterol transport, it is tempting to speculate that perturbed intracellular trafficking is involved in the increased intraneuronal A beta aggregation in AD."],["dc.identifier.doi","10.1007/s00401-010-0666-1"],["dc.identifier.isi","000276353400003"],["dc.identifier.pmid","20217101"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?goescholar/4175"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19930"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0001-6322"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Accumulation of intraneuronal A beta correlates with ApoE4 genotype"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Acta neuropathologica communications"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","Kalimo, Hannu"],["dc.contributor.author","Lalowski, Maciej"],["dc.contributor.author","Bogdanovic, Nenad"],["dc.contributor.author","Philipson, Ola"],["dc.contributor.author","Bird, Thomas D."],["dc.contributor.author","Nochlin, David"],["dc.contributor.author","Schellenberg, Gerard D."],["dc.contributor.author","Brundin, Rosemarie"],["dc.contributor.author","Olofsson, Tommie"],["dc.contributor.author","Soliymani, Rabah"],["dc.contributor.author","Baumann, Marc"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Bayer, Thomas A."],["dc.contributor.author","Nilsson, Lars"],["dc.contributor.author","Basun, Hans"],["dc.contributor.author","Lannfelt, Lars"],["dc.contributor.author","Ingelsson, Martin"],["dc.date.accessioned","2019-07-09T11:42:19Z"],["dc.date.available","2019-07-09T11:42:19Z"],["dc.date.issued","2013"],["dc.description.abstract","BACKGROUND: The Arctic mutation (p.E693G/p.E22G)fs within the β-amyloid (Aβ) region of the β-amyloid precursor protein gene causes an autosomal dominant disease with clinical picture of typical Alzheimer's disease. Here we report the special character of Arctic AD neuropathology in four deceased patients. RESULTS: Aβ deposition in the brains was wide-spread (Thal phase 5) and profuse. Virtually all parenchymal deposits were composed of non-fibrillar, Congo red negative Aβ aggregates. Congo red only stained angiopathic vessels. Mass spectrometric analyses showed that Aβ deposits contained variably truncated and modified wild type and mutated Aβ species. In three of four Arctic AD brains, most cerebral cortical plaques appeared targetoid with centres containing C-terminally (beyond aa 40) and variably N-terminally truncated Aβ surrounded by coronas immunopositive for Aβx-42. In the fourth patient plaque centres contained almost no Aβ making the plaques ring-shaped. The architectural pattern of plaques also varied between different anatomic regions. Tau pathology corresponded to Braak stage VI, and appeared mainly as delicate neuropil threads (NT) enriched within Aβ plaques. Dystrophic neurites were scarce, while neurofibrillary tangles were relatively common. Neuronal perikarya within the Aβ plaques appeared relatively intact. CONCLUSIONS: In Arctic AD brain differentially truncated abundant Aβ is deposited in plaques of variable numbers and shapes in different regions of the brain (including exceptional targetoid plaques in neocortex). The extracellular non-fibrillar Aβ does not seem to cause overt damage to adjacent neurons or to induce formation of neurofibrillary tangles, supporting the view that intracellular Aβ oligomers are more neurotoxic than extracellular Aβ deposits. However, the enrichment of NTs within plaques suggests some degree of intra-plaque axonal damage including accumulation of hp-tau, which may impair axoplasmic transport, and thereby contribute to synaptic loss. Finally, similarly as the cotton wool plaques in AD resulting from exon 9 deletion in the presenilin-1 gene, the Arctic plaques induced only modest glial and inflammatory tissue reaction."],["dc.identifier.doi","10.1186/2051-5960-1-60"],["dc.identifier.fs","599195"],["dc.identifier.pmid","24252272"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58642"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2051-5960"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","The Arctic AβPP mutation leads to Alzheimer's disease pathology with highly variable topographic deposition of differentially truncated Aβ."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1181"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Journal of Neural Transmission"],["dc.bibliographiccitation.lastpage","1187"],["dc.bibliographiccitation.volume","115"],["dc.contributor.author","Kessler, Holger"],["dc.contributor.author","Bayer, Thomas A."],["dc.contributor.author","Bach, Daniela"],["dc.contributor.author","Schneider-Axmann, Thomas"],["dc.contributor.author","Supprian, Tillmann"],["dc.contributor.author","Herrmann, Wolfgang"],["dc.contributor.author","Haber, Manfred"],["dc.contributor.author","Multhaup, Gerd"],["dc.contributor.author","Falkai, Peter"],["dc.contributor.author","Pajonk, Frank-Gerald B."],["dc.date.accessioned","2018-11-07T11:12:34Z"],["dc.date.available","2018-11-07T11:12:34Z"],["dc.date.issued","2008"],["dc.description.abstract","Disturbed copper (Cu) homeostasis may be associated with the pathological processes in Alzheimer's disease (AD). In the present report, we evaluated the efficacy of oral Cu supplementation in the treatment of AD in a prospective, randomized, double-blind, placebo-controlled phase 2 clinical trial in patients with mild AD for 12 months. Sixty-eight subjects were randomized. The treatment was well-tolerated. There were however no significant differences in primary outcome measures (Alzheimer's Disease Assessment Scale, Cognitive subscale, Mini Mental Status Examination) between the verum [Cu-(II)-orotate-dihydrate; 8 mg Cu daily] and the placebo group. Despite a number of findings supporting the hypothesis of environmental Cu modulating AD, our results demonstrate that oral Cu intake has neither a detrimental nor a promoting effect on the progression of AD."],["dc.description.sponsorship","HOMFOR program of the Saarland University Medical Faculty"],["dc.identifier.doi","10.1007/s00702-008-0080-1"],["dc.identifier.isi","000258539500012"],["dc.identifier.pmid","18587525"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?goescholar/3559"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53696"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Wien"],["dc.relation.issn","0300-9564"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Intake of copper has no effect on cognition in patients with mild Alzheimer's disease: a pilot phase 2 clinical trial"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","24"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Acta Neuropathologica Communications"],["dc.bibliographiccitation.lastpage","12"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Reinert, Jochim"],["dc.contributor.author","Richard, Bernhard C."],["dc.contributor.author","Klafki, Hans W."],["dc.contributor.author","Friedrich, Beate"],["dc.contributor.author","Bayer, Thomas A."],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Kovacs, Gabor G."],["dc.contributor.author","Ingelsson, Martin"],["dc.contributor.author","Lannfelt, Lars"],["dc.contributor.author","Paetau, Anders"],["dc.contributor.author","Bergquist, Jonas"],["dc.contributor.author","Wirths, Oliver"],["dc.date.accessioned","2017-09-07T11:44:29Z"],["dc.date.available","2017-09-07T11:44:29Z"],["dc.date.issued","2016"],["dc.description.abstract","In Alzheimer’s disease (AD) a variety of amyloid β-peptides (Aβ) are deposited in the form of extracellular diffuse and neuritic plaques (NP), as well as within the vasculature. The generation of Aβ from its precursor, the amyloid precursor protein (APP), is a highly complex procedure that involves subsequent proteolysis of APP by β- and γ-secretases. Brain accumulation of Aβ due to impaired Aβ degradation and/or altered ratios between the different Aβ species produced is believed to play a pivotal role in AD pathogenesis. While the presence of Aβ40 and Aβ42 in vascular and parenchymal amyloid have been subject of extensive studies, the deposition of carboxyterminal truncated Aβ peptides in AD has not received comparable attention. In the current study, we for the first time demonstrate the immunohistochemical localization of Aβ37 and Aβ39 in human sporadic AD (SAD). Our study further included the analysis of familial AD (FAD) cases carrying the APP mutations KM670/671NL, E693G and I716F, as well as a case of the PSEN1 ΔExon9 mutation. Aβ37 and Aβ39 were found to be widely distributed within the vasculature in the brains of the majority of studied SAD and FAD cases, the latter also presenting considerable amounts of Aβ37 containing NPs. In addition, both peptides were found to be present in extracellular plaques but only scarce within the vasculature in brains of a variety of transgenic AD mouse models. Taken together, our study indicates the importance of C-terminally truncated Aβ in sporadic and familial AD and raises questions about how these species are generated and regulated."],["dc.identifier.doi","10.1186/s40478-016-0294-7"],["dc.identifier.gro","3151681"],["dc.identifier.pmid","26955942"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12971"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8499"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","public"],["dc.notes.submitter","chake"],["dc.relation.issn","2051-5960"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Deposition of C-terminally truncated Aβ species Aβ37 and Aβ39 in Alzheimer’s disease and transgenic mouse models"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","913"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Journal of Neural Transmission"],["dc.bibliographiccitation.lastpage","920"],["dc.bibliographiccitation.volume","116"],["dc.contributor.author","Marcello, Andrea"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Schneider-Axmann, Thomas"],["dc.contributor.author","Degerman-Gunnarsson, Malin"],["dc.contributor.author","Lannfelt, Lars"],["dc.contributor.author","Bayer, Thomas"],["dc.date.accessioned","2019-07-09T11:52:23Z"],["dc.date.available","2019-07-09T11:52:23Z"],["dc.date.issued","2009"],["dc.description.abstract","It has previously been shown that immune complexes (IC) of a given biomarker with class M immunoglobulins (IgM) provide better performances compared to the unbound biomarker in a number of cancer entities. In the present work, we investigated IC of IgM-Aβ as a potential biomarker for Alzheimer’s disease (AD). Aβ–IgM concentration has been measured in 75 plasma samples from patients with AD, individuals with mild cognitive impairment (MCI), and healthy age- and sex-matched controls (HC). To characterize the fractions associated with Aβ, pooled plasma samples were subjected to gel-filtration analysis. Size-separated fractions were analyzed for the presence of Aβ using a sandwich ELIp. assay. A strong reactivity was observed in the high molecular weight IgM (>500 kDa) and 150 kDa (IgG) fractions indicating that blood Aβ is strongly associated with antibodies. Using an ELISA assay detecting Aβ–IgM complexes, we observed that high levels of Aβ–IgMs were detectable in HC and MCI patients; however, there was no significant difference to the AD group."],["dc.identifier.doi","10.1007/s00702-009-0224-y"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?goescholar/3557"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60171"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Springer"],["dc.publisher.place","Vienna"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Circulating immune complexes of Aβ and IgM in plasma of patients with Alzheimer’s disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","7"],["dc.bibliographiccitation.journal","Open Longevity Science"],["dc.bibliographiccitation.lastpage","12"],["dc.bibliographiccitation.volume","2"],["dc.contributor.author","Wirths, O."],["dc.contributor.author","Bayer, T. A."],["dc.date.accessioned","2011-09-28T16:39:26Z"],["dc.date.accessioned","2021-10-27T13:11:11Z"],["dc.date.available","2011-09-28T16:39:26Z"],["dc.date.available","2021-10-27T13:11:11Z"],["dc.date.issued","2008"],["dc.description.abstract","Whereas a plethora of studies focusses on extracellular plaque deposition, only a very limited amount of reports deal with intraneuronal accumulation of A􀀂 peptides in human AD. However, over the past years, accumulating evidence points to a significant role of intraneuronal A􀀂 triggering the pathological cascade leading to neurodegeneration in Alzheimer’s disease (AD). Much of the data originate from studies on transgenic mouse models of AD, where initial intraneuronal A􀀂 accumulation which predes extracellular plaque deposition, has been repeatedly reported. The current review discusses the impact of this finding on the future development of novel mouse models for preclinical research as a basis for therapeutic intervention."],["dc.identifier.doi","10.2174/1876326X00802010007"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6974"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/91567"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.orgunit","Fakultät für Biologie und Psychologie"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","570"],["dc.title","Early Intraneuronal Beta-Amyloid Pathology: Do Transgenic Mice Represent Valid Model Systems?"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Medicine"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Franke, Timon N."],["dc.contributor.author","Irwin, Caroline"],["dc.contributor.author","Bayer, Thomas A."],["dc.contributor.author","Brenner, Winfried"],["dc.contributor.author","Beindorff, Nicola"],["dc.contributor.author","Bouter, Caroline"],["dc.contributor.author","Bouter, Yvonne"],["dc.date.accessioned","2021-04-14T08:32:38Z"],["dc.date.available","2021-04-14T08:32:38Z"],["dc.date.issued","2020"],["dc.description.abstract","Imaging biomarkers of Alzheimer's disease (AD) that are able to detect molecular changes in vivo and transgenic animal models mimicking AD pathologies are essential for the evaluation of new therapeutic strategies. Positron-emission tomography (PET) using either 18F-Fluorodeoxyglucose (18F-FDG) or amyloid-tracers is a well-established, non-invasive tool in the clinical diagnostics of AD assessing two major pathological hallmarks. 18F-FDG-PET is able to detect early changes in cerebral glucose metabolism and amyloid-PET shows cerebral amyloid load. However, the suitability of 18F-FDG- and amyloid-PET in the widely used 5XFAD mouse model of AD is unclear as only a few studies on the use of PET biomarkers are available showing some conflicting results. The aim of this study was the evaluation of 18F-FDG-PET and amyloid-PET in 5XFAD mice in comparison to neurological deficits and neuropathological changes. Seven- and 12-month-old male 5XFAD mice showed a significant reduction in brain glucose metabolism in 18F-FDG-PET and amyloid-PET with 18F-Florbetaben demonstrated an increased cerebral amyloid deposition (n = 4–6 per group). Deficits in spatial reference memory were detected in 12-month-old 5XFAD mice in the Morris Water Maze (n = 10–12 per group). Furthermore, an increased plaque load and gliosis could be proven immunohistochemically in 5XFAD mice (n = 4–6 per group). PET biomarkers 18F-FDG and 18F-Florbetaben detected cerebral hypometabolism and increased plaque load even before the onset of severe memory deficits. Therefore, the 5XFAD mouse model of AD is well-suited for in vivo monitoring of AD pathologies and longitudinal testing of new therapeutic approaches."],["dc.identifier.doi","10.3389/fmed.2020.00529"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17550"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83972"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","2296-858X"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","In vivo Imaging With 18F-FDG- and 18F-Florbetaben-PET/MRI Detects Pathological Changes in the Brain of the Commonly Used 5XFAD Mouse Model of Alzheimer's Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]