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1,123 results on '"Herms, Jochen"'

205. L-type amino acid transporter (LAT) 1 expression in 18F-FET-negative gliomas.

Author

Vettermann, Franziska J., Diekmann, Caroline, Weidner, Lorraine, Unterrainer, Marcus, Suchorska, Bogdana, Ruf, Viktoria, Dorostkar, Mario, Wenter, Vera, Herms, Jochen, Tonn, Jörg-Christian, Bartenstein, Peter, Riemenschneider, Markus J., and Albert, Nathalie L.

Subjects
GLIOMAS, AMINO acids, ASTROCYTOMAS, GENETIC overexpression, DIAGNOSIS
Abstract

Background: O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) is a highly sensitive PET tracer for glioma imaging, and its uptake is suggested to be driven by an overexpression of the L-type amino-acid transporter 1 (LAT1). However, 30% of low- and 5% of high-grade gliomas do not present enhanced 18F-FET uptake at primary diagnosis ("18F-FET-negative gliomas") and the pathophysiologic basis for this phenomenon remains unclear. The aim of this study was to determine the expression of LAT1 in a homogeneous group of newly diagnosed 18F-FET-negative gliomas and to compare them to a matched group of 18F-FET-positive gliomas. Forty newly diagnosed IDH-mutant astrocytomas without 1p/19q codeletion were evaluated (n = 20 18F-FET-negative (tumour-to-background ratio (TBR) < 1.6), n = 20 18F-FET-positive gliomas (TBR > 1.6)). LAT1 immunohistochemistry (IHC) was performed using SLC7A5/LAT1 antibody. The percentage of LAT1-positive tumour cells (%) and the staining intensity (range 0–2) were multiplied to an overall score (H-score; range 0–200) and correlated to PET findings as well as progression-free survival (PFS). Results: IHC staining of LAT1 expression was positive in both, 18F-FET-positive as well as 18F-FET-negative gliomas. No differences were found between the 18F-FET-negative and 18F-FET-positive group with regard to percentage of LAT1-positive tumour cells, staining intensity or H-score. Interestingly, the LAT1 expression showed a significant negative correlation with the PFS (p = 0.031), whereas no significant correlation was found for TBRmax, neither in the overall group nor in the 18F-FET-positive group only (p = 0.651 and p = 0.140). Conclusion: Although LAT1 is reported to mediate the uptake of 18F-FET into tumour cells, the levels of LAT1 expression do not correlate with the levels of 18F-FET uptake in IDH-mutant astrocytomas. In particular, the lack of tracer uptake in 18F-FET-negative gliomas cannot be explained by a reduced LAT1 expression. A higher LAT1 expression in IDH-mutant astrocytomas seems to be associated with a short PFS. Further studies regarding mechanisms influencing the uptake of 18F-FET are necessary. [ABSTRACT FROM AUTHOR]

Published
2021
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206. Prediction of TERTp-mutation status in IDH-wildtype high-grade gliomas using pre-treatment dynamic [18F]FET PET radiomics.

Author

Li, Zhicong, Kaiser, Lena, Holzgreve, Adrien, Ruf, Viktoria C., Suchorska, Bogdana, Wenter, Vera, Quach, Stefanie, Herms, Jochen, Bartenstein, Peter, Tonn, Jörg-Christian, Unterrainer, Marcus, and Albert, Nathalie L.

Subjects
RECEIVER operating characteristic curves, RADIOMICS, FEATURE extraction, ASTROCYTOMAS, POSITRON emission tomography, GLIOMAS
Abstract

Purpose: To evaluate radiomic features extracted from standard static images (20–40 min p.i.), early summation images (5–15 min p.i.), and dynamic [18F]FET PET images for the prediction of TERTp-mutation status in patients with IDH-wildtype high-grade glioma. Methods: A total of 159 patients (median age 60.2 years, range 19–82 years) with newly diagnosed IDH-wildtype diffuse astrocytic glioma (WHO grade III or IV) and dynamic [18F]FET PET prior to surgical intervention were enrolled and divided into a training (n = 112) and a testing cohort (n = 47) randomly. First-order, shape, and texture radiomic features were extracted from standard static (20–40 min summation images; TBR20–40), early static (5–15 min summation images; TBR5–15), and dynamic (time-to-peak; TTP) images, respectively. Recursive feature elimination was used for feature selection by 10-fold cross-validation in the training cohort after normalization, and logistic regression models were generated using the radiomic features extracted from each image to differentiate TERTp-mutation status. The areas under the ROC curve (AUC), accuracy, sensitivity, specificity, and positive and negative predictive value were calculated to illustrate diagnostic power in both the training and testing cohort. Results: The TTP model comprised nine selected features and achieved highest predictability of TERTp-mutation with an AUC of 0.82 (95% confidence interval 0.71–0.92) and sensitivity of 92.1% in the independent testing cohort. Weak predictive capability was obtained in the TBR5–15 model, with an AUC of 0.61 (95% CI 0.42–0.80) in the testing cohort, while no predictive power was observed in the TBR20–40 model. Conclusions: Radiomics based on TTP images extracted from dynamic [18F]FET PET can predict the TERTp-mutation status of IDH-wildtype diffuse astrocytic high-grade gliomas with high accuracy preoperatively. [ABSTRACT FROM AUTHOR]

Published
2021
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207. Glitter in the Darkness? Non-fibrillar β-amyloid Plaque Components Significantly Impact the β-amyloid PET Signal in Mouse Models of Alzheimer’s Disease.

Author

Biechele, Gloria, Monasor, Laura Sebastian, Wind, Karin, Blume, Tanja, Parhizkar, Samira, Arzberger, Thomas, Sacher, Christian, Beyer, Leonie, Eckenweber, Florian, Gildehaus, Franz-Josef, Ungern-Sternberg, Barbara von, Willem, Michael, Bartenstein, Peter, Cumming, Paul, Rominger, Axel, Herms, Jochen, Lichtenthaler, Stefan F., Haass, Christian, Tahirovic, Sabina, and Brendel, Matthias

Published
2021
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208. The cellular prion protein binds copper in vivo

Author

Brown, David R., Qin, Kefeng, Herms, Jochen W., Madlung, Axel, Manson, Jean, Strome, Robert, Fraser, Paul E., Kruck, Theo, von Bohlen, Alex, Schulz-Schaeffer, Walter, Giese, Armin, Westaway, David, and Kretzschmar, Hans

Published
1997
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210. Early and longitudinal microglial activation but not amyloid accumulation predict cognitive outcome in PS2APP mice

Author

Focke, Carola, Blume, Tanja, Zott, Benedikt, Shi, Yuan, Deussing, Maximilian, Peters, Finn, Schmidt, Claudio, Kleinberger, Gernot, Lindner, Simon, Gildehaus, Franz-Josef, Beyer, Leonie, Von Ungern-Sternberg, Barbara, Bartenstein, Peter, Ozmen, Laurence, Baumann, Karlheinz, Dorostkar, Mario M, Haass, Christian, Adelsberger, Helmuth, Herms, Jochen, Rominger, Axel Oliver, and Brendel, Matthias

Subjects
610 Medicine & health
Abstract

Neuroinflammation may have beneficial or detrimental net effects on the cognitive outcome of Alzheimer's disease patients (AD). 18kDa translocator protein (TSPO) imaging by positron-emission-tomography (PET) enables longitudinal monitoring of microglial activation in vivo. We compiled serial PET measures of TSPO and amyloid with terminal cognitive assessment (water maze) in an AD transgenic mouse model (PS2APP) from eight to 13 months of age, followed by immunohistochemical analyses of microglia, amyloid and synaptic density. Better cognitive outcome and higher synaptic density in PS2APP mice was predicted by higher TSPO expression at eight months. The progression of TSPO activation to 13 months also showed a moderate association with spared cognition, but amyloidosis did not correlate with the cognitive outcome, regardless of the timepoint. This first PET investigation with longitudinal TSPO- and amyloid-PET together with terminal cognitive testing in an AD mouse model indicates that continuing microglial response seems to impart preserved cognitive performance.

Published
2019
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211. Increasing fibrillar amyloidosis is associated with improved cognition and synaptic preservation caused by microglia modulation

Author

Shi, Yuan, Kleinberger, Gernot, Haass, Christian, and Herms, Jochen

Abstract

Aim: Immunmodulatory treatment with the PPARγ agonist Pioglitazone shows heterogeneous results in Alzheimer`s disease (AD). We aimed to apply longitudinal in-vivo PET monitoring combined with terminal cognitive assessment to investigate PET as a tool for longitudinal monitoring of treatment effects and to establish efficacy determinants.Methods: PS2APP (TG) mice and C57Bl/6 (WT) mice were randomly stratified in Pioglitazone (N=13 TG, N=8 WT) and placebo treatment (N=10 TG, N=7 WT) at the age of 8 months. Therapy was conducted for 5 months (mo). All mice received amyloid-PET (Aβ-PET) scans (F-18-Florbetaben) at baseline and after 5 mo, to investigate progression of plaque load. TSPO-PET (F-18-GE180) was performed at baseline, after 0.5 mo, 2.5 mo and 5 mo to analyze changes in microglial activation. Forebrain PET signals were assessed for each timepoint. Behavioral testing after the terminal PET scan was followed by molecular validation including immunohistochemical (IHC) and profiling of microglia phenotypes, plaque composition and synaptic density.Results: Pioglitazone treatment resulted in a reduction of -13% (p < 0.001) in the TSPO-PET signal as well as an unexpected increase of Aβ-PET in the treatment group compared to placebo (+16% vs. +13%; p < 0.05; supporting Fig. a) for the entire monitoring period. IHC proved Aβ-PET results and showed more fibrillar plaque load in the treatment group (4.2% vs 2.8%, p < 0.05; Fig. b). Nonetheless, we observed improved cognitive performance (escape latency 3.2 vs. 4.8 seconds, p < 0.05) and attenuated synaptic loss (0.43 vs. 0.38 VGLUT1/µm2, p < 0.001) after treatment. Importantly, we discovered a direct correlation between Aβ-PET increase with TSPO decrease (R=0.62; p < 0.05) and improved cognitive outcome (R=0.39 p < 0.05). IHC revealed, that dense proportions of the Aβ plaque raised during treatment, whereas looser parts of Aβ plaques decreased. Genetic analyses indicated a treatment dependent change in microglial gene signature (Fig. c).Conclusions: Reduction of microglial activation by Pioglitazone anti-inflammatory treatment is associated with increasing fibrillar Aβ. However, this shift of loose to more dense proportions of Aβ plaques is accompanied by improved cognitive performance and attenuated synaptic loss after treatment. This finding has strong implications to Pioglitazone treatment monitoring by Aβ-PET as a signal increase over time could be misinterpreted as a treatment failure. Furthermore, this indicates for the first time that increasing fibrillar amyloidosis can preserve cognition.

Published
2019

217. Superiority of Formalin-Fixed Paraffin-Embedded Brain Tissue for in vitro Assessment of Progressive Supranuclear Palsy Tau Pathology With [ 18 F]PI-2620.

Author

Willroider, Marie, Roeber, Sigrun, Horn, Anja K. E., Arzberger, Thomas, Scheifele, Maximilian, Respondek, Gesine, Sabri, Osama, Barthel, Henryk, Patt, Marianne, Mishchenko, Olena, Schildan, Andreas, Mueller, André, Koglin, Norman, Stephens, Andrew, Levin, Johannes, Höglinger, Günter U., Bartenstein, Peter, Herms, Jochen, Brendel, Matthias, and Beyer, Leonie

Subjects
PROGRESSIVE supranuclear palsy, TAU proteins, POSITRON emission tomography, ALZHEIMER'S patients, AUTORADIOGRAPHY
Abstract

Objectives: Autoradiography on brain tissue is used to validate binding targets of newly discovered radiotracers. The purpose of this study was to correlate quantification of autoradiography signal using the novel next-generation tau positron emission tomography (PET) radiotracer [18F]PI-2620 with immunohistochemically determined tau-protein load in both formalin-fixed paraffin-embedded (FFPE) and frozen tissue samples of patients with Alzheimer's disease (AD) and Progressive Supranuclear Palsy (PSP). Methods: We applied [18F]PI-2620 autoradiography to postmortem cortical brain samples of six patients with AD, five patients with PSP and five healthy controls, respectively. Binding intensity was compared between both tissue types and different disease entities. Autoradiography signal quantification (CWMR = cortex to white matter ratio) was correlated with the immunohistochemically assessed tau load (AT8-staining, %-area) for FFPE and frozen tissue samples in the different disease entities. Results: In AD tissue, relative cortical tracer binding was higher in frozen samples when compared to FFPE samples (CWMRfrozen vs. CWMRFFPE: 2.5-fold, p < 0.001), whereas the opposite was observed in PSP tissue (CWMRfrozen vs. CWMRFFPE: 0.8-fold, p = 0.004). In FFPE samples, [18F]PI-2620 autoradiography tracer binding and immunohistochemical tau load correlated significantly for both PSP (R = 0.641, p < 0.001) and AD tissue (R = 0.435, p = 0.016), indicating a high agreement of relative tracer binding with underlying pathology. In frozen tissue, the correlation between autoradiography and immunohistochemistry was only present in AD (R = 0.417, p = 0.014) but not in PSP tissue (R = −0.115, p = n.s.). Conclusion: Our head-to-head comparison indicates that FFPE samples show superiority over frozen samples for autoradiography assessment of PSP tau pathology by [18F]PI-2620. The [18F]PI-2620 autoradiography signal in FFPE samples reflects AT8 positive tau in samples of both PSP and AD patients. [ABSTRACT FROM AUTHOR]

Published
2021
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218. Contribution of the astrocytic tau pathology to synapse loss in progressive supranuclear palsy and corticobasal degeneration.

Author

Briel, Nils, Pratsch, Katrin, Roeber, Sigrun, Arzberger, Thomas, and Herms, Jochen

Subjects
PROGRESSIVE supranuclear palsy, TAU proteins, FRONTOTEMPORAL lobar degeneration, SYNAPSES, NEURAL transmission, THERAPEUTICS
Abstract

Primary 4‐repeat tauopathies with frontotemporal lobar degeneration (FTLD) like Progressive Supranuclear Palsy (PSP) or Corticobasal Degeneration (CBD) show diverse cellular pathology in various brain regions. Besides shared characteristics of neuronal and oligodendroglial cytoplasmic inclusions of accumulated hyperphosphorylated tau protein (pTau), astrocytes in PSP and CBD contain pathognomonic pTau aggregates — hence, lending the designation tufted astrocytes (TA) or astrocytic plaques (AP), respectively. pTau toxicity is most commonly assigned to neurons, whereas the implications of astrocytic pTau for maintaining neurotransmission within the tripartite synapse of human brains is not well understood. We performed immunofluorescent synapse labeling and automated puncta quantification in the medial frontal gyrus (MFG) and striatal regions from PSP and CBD postmortem samples to capture morphometric synaptic alterations. This approach indicated general synaptic losses of both, excitatory and inhibitory bipartite synapses in the frontal cortex of PSP cases, whereas in CBD lower synapse densities were only related to astrocytic plaques. In contrast to tufted astrocytes in PSP, affected astrocytes in CBD could not preserve synaptic integrity within their spatial domains, when compared to non‐affected internal astrocytes or astrocytes in healthy controls. These findings suggest a pTau pathology‐associated role of astrocytes in maintaining connections within neuronal circuits, considered as the microscopic substrate of cognitive dysfunction in CBD. By contrasting astrocytic‐synaptic associations in both diseases, we hereby highlight astrocytic pTau as an important subject of prospective research and as a potential cellular target for therapeutic approaches in the primary tauopathies PSP and CBD. [ABSTRACT FROM AUTHOR]

Published
2021
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225. TERT-Promoter Mutational Status in Glioblastoma – Is There an Association With Amino Acid Uptake on Dynamic 18F-FET PET?

Author

Unterrrainer, Marcus, Ruf, Viktoria, von Rohr, Katharina, Suchorska, Bogdana, Mittlmeier, Lena Maria, Beyer, Leonie, Brendel, Matthias, Wenter, Vera, Kunz, Wolfgang G., Bartenstein, Peter, Herms, Jochen, Niyazi, Maximilian, Tonn, Jörg C., and Albert, Nathalie Lisa

Subjects
TELOMERASE reverse transcriptase, AMINO acids, GLIOBLASTOMA multiforme, BRAIN tumors
Abstract

Objective: The mutation of the 'telomerase reverse transcriptase gene promoter' (TERTp) has been identified as an important factor for individual prognostication and tumorigenesis and will be implemented in upcoming glioma classifications. Uptake characteristics on dynamic 18F-FET PET have been shown to serve as additional imaging biomarker for prognosis. However, data on the correlation of TERTp-mutational status and amino acid uptake on dynamic 18F-FET PET are missing. Therefore, we aimed to analyze whether static and dynamic 18F-FET PET parameters are associated with the TERTp-mutational status in de-novo IDH -wildtype glioblastoma and whether a TERTp-mutation can be predicted by dynamic 18F-FET PET. Methods: Patients with de-novo IDH -wildtype glioblastoma, WHO grade IV, available TERTp-mutational status and dynamic 18F-FET PET scan prior to any therapy were included. Here, established clinical parameters maximal and mean tumor-to-background-ratios (TBRmax/TBRmean), the biological-tumor-volume (BTV) and minimal-time-to-peak (TTPmin) on dynamic PET were analyzed and correlated with the TERTp-mutational status. Results: One hundred IDH -wildtype glioblastoma patients were evaluated; 85/100 of the analyzed tumors showed a TERTp-mutation (C228T or C250T), 15/100 were classified as TERTp-wildtype. None of the static PET parameters was associated with the TERTp-mutational status (median TBRmax 3.41 vs. 3.32 (p=0.362), TBRmean 2.09 vs. 2.02 (p=0.349) and BTV 26.1 vs. 22.4 ml (p=0.377)). Also, the dynamic PET parameter TTPmin did not differ in both groups (12.5 vs. 12.5 min, p=0.411). Within the TERTp-mutant subgroups (i.e., C228T (n=23) & C250T (n=62)), the median TBRmax (3.33 vs. 3.69, p=0.095), TBRmean (2.08 vs. 2.09, p=0.352), BTV (25.4 vs. 30.0 ml, p=0.130) and TTPmin (12.5 vs. 12.5 min, p=0.190) were comparable, too. Conclusion: Uptake characteristics on dynamic 18F-FET PET are not associated with the TERTp-mutational status in glioblastoma However, as both, dynamic 18F-FET PET parameters as well as the TERTp-mutation status are well-known prognostic biomarkers, future studies should investigate the complementary and independent prognostic value of both factors in order to further stratify patients into risk groups. [ABSTRACT FROM AUTHOR]

Published
2021
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226. Comparison of 18F-T807 and 18F-THK5117 PET in a Mouse Model of Tau Pathology

Author

Brendel, Matthias, Yousefi, Behrooz H, Bartenstein, Peter, Haass, Christian, Okamura, Nobuyuki, Herms, Jochen, Yakushev, Igor, Rominger, Axel, Blume, Tanja, Herz, Michael, Focke, Carola, Deussing, Maximilian, Peters, Finn, Lindner, Simon, von Ungern-Sternberg, Barbara, and Drzezga, Alexander

Subjects
ddc:610
Abstract

Comparison of 18F-T807 and 18F-THK5117 PET in a Mouse Model of Tau Pathology.

Published
2018

227. Additional file 4: of The Trem2 R47H Alzheimer’s risk variant impairs splicing and reduces Trem2 mRNA and protein in mice but not in humans

Author

Xianyuan Xiang, Piers, Thomas, Wefers, Benedikt, Kaichuan Zhu, Mallach, Anna, Brunner, Bettina, Kleinberger, Gernot, Song, Wilbur, Colonna, Marco, Herms, Jochen, Wurst, Wolfgang, Pocock, Jennifer, and Haass, Christian

Abstract

Figure S3. iMG differentiation and validation. a Schematic of the in vitro differentiation of iPSC-derived microglia-like cells (iMG). (i): Human iPSCs are grown in feeder free conditions with no spontaneous differentiation. Scale bar: 250 μm. (ii): Embryoid bodies are formed in the presence of 3 factors SCF, BMP4, and VEGF; Scale bar: 750 μm. (iii): Myeloid cells are generated after culturing with IL3 and MCSF growth factors for 3–4 weeks, then stained for classic myeloid/macrophage markers CD68. Scale bar: 50 μm. (iv): Further differentiation to microglia-like cells that positive for microglial markers P2RY12. Scale bar: 20 μm. (v): Addition of the two final factors (CD200 and CX3CL1) matures the iMG. Scale bar: 20 μm. b Heat map showing mRNA expression of a microglial gene signature in iMG, human monocyte-derived macrophages (hMac), human primary microglia (hMG), and iPSC samples. Clear clustering is observed between iMG and hMG. (PDF 159 kb)

Published
2018
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228. Additional file 3: of The Trem2 R47H Alzheimerâ s risk variant impairs splicing and reduces Trem2 mRNA and protein in mice but not in humans

Author

Xianyuan Xiang, Piers, Thomas, Wefers, Benedikt, Kaichuan Zhu, Mallach, Anna, Brunner, Bettina, Kleinberger, Gernot, Song, Wilbur, Colonna, Marco, Herms, Jochen, Wurst, Wolfgang, Pocock, Jennifer, and Haass, Christian

Abstract

Figure S2. Sequence of the aberrantly spliced murine Trem2 mRNA. Trem2 gene sequence. Exon in black; intron in green; // indicates splicing sites. (PDF 93 kb)

Published
2018
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229. Additional file 2: of The Trem2 R47H Alzheimerâ s risk variant impairs splicing and reduces Trem2 mRNA and protein in mice but not in humans

Author

Xianyuan Xiang, Piers, Thomas, Wefers, Benedikt, Kaichuan Zhu, Mallach, Anna, Brunner, Bettina, Kleinberger, Gernot, Song, Wilbur, Colonna, Marco, Herms, Jochen, Wurst, Wolfgang, Pocock, Jennifer, and Haass, Christian

Subjects
body regions, nervous system, fungi
Abstract

Table S1. Allele specific quantitative PCR for Trem2 R47H knock-in mice (PDF 92 kb)

Published
2018
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230. Additional file 5: of The Trem2 R47H Alzheimerâ s risk variant impairs splicing and reduces Trem2 mRNA and protein in mice but not in humans

Author

Xianyuan Xiang, Piers, Thomas, Wefers, Benedikt, Kaichuan Zhu, Mallach, Anna, Brunner, Bettina, Kleinberger, Gernot, Song, Wilbur, Colonna, Marco, Herms, Jochen, Wurst, Wolfgang, Pocock, Jennifer, and Haass, Christian

Subjects
body regions, nervous system, fungi
Abstract

Table S2. Allele specific quantitative PCR for iMG and patient brains (PDF 104 kb)

Published
2018
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231. Microglial Response to Increasing Amyloidosis Saturates During Aging of an Alzheimer's Disease Mouse Model

Author

Herms, Jochen

Abstract

Objectives: We previously established dual tracer PET imaging of β-amyloid (Aβ) and activated microglia in Alzheimer’s disease (AD) mouse models. Associations between both biomarkers during disease progression of AD are still discussed controversially. The aim of the present longitudinal study was to enlighten the longitudinal association between Aβ and microglial response during aging of APPSL70 mice, an amyloid mouse model, in vivo. A variant baseline age enabled us to perform correlation analysis with the longitudinal biomarker progression over seven months by dual tracer PET. Terminal immunohistochemistry served for interpretation of PET results under consideration of findings at individual plaque and cell level.Methods: APPSL70 mice (N=17; starting age: 15-38 weeks) and age-matched C57Bl/6 controls (WT) were investigated in a longitudinal design using amyloid (18F-florbetaben) and 18kDa translocator protein (TSPO) PET (18F-GE180). PET was performed at baseline (0 weeks), intermediate (+10 weeks) and terminal (+26 weeks) time points. A frontal cortical volume-of-interest (VOI) with hindbrain white matter reference served for calculation of standardized-uptake-value ratio (SUVRCTX/WM) values. Terminal percentage differences were calculated relative to baseline (Δ-%). Additionally, Z-scores versus WT were calculated for amyloid-PET and TSPO-PET, and the microglial activation relative to amyloidosis was defined as the Z-score difference (TSPO - Aβ). Immunohistochemistry for activated microglia (Iba-1) and fibrillar Aβ (methoxy-X04) were performed with 3D stacks to analyze brain volumes of microglial activation relative to the plaque size and the distance to plaque borders. Results: Relative to the baseline age, an exponential function of Δ-% SUVRCTX/WM was observed in Aβ-PET of APPSL70 mice. Contrary an inverse U-shape was present for Δ-% SUVRCTX/WM of TSPO-PET with a peak increase at a baseline age of 28 weeks. Longitudinal Z-score differences dropped with aging, meaning that less microglial response was observed relative to ongoing amyloidosis in aging APPSL70 mice. Immunohistochemistry revealed that the fraction of activated microglia at the plaque border decreased with increasing plaque size, while the plaque size was associated with age. IBA-1 positive cells in regions without Aβ plaques were significantly lower in APPSL70 mice when compared to WT. Conclusions: Microglial activity decreases relative to ongoing amyloidosis during aging of APPSL70 mice. The plaque-associated microglial fraction showed saturation and correlated with plaque size and aging, most likely related to limited proliferation of microglia, emptying the peripheral reserve.

Published
2018

232. Additional file 1: of The Trem2 R47H Alzheimer’s risk variant impairs splicing and reduces Trem2 mRNA and protein in mice but not in humans

Author

Xianyuan Xiang, Piers, Thomas, Wefers, Benedikt, Kaichuan Zhu, Mallach, Anna, Brunner, Bettina, Kleinberger, Gernot, Song, Wilbur, Colonna, Marco, Herms, Jochen, Wurst, Wolfgang, Pocock, Jennifer, and Haass, Christian

Abstract

Figure S1. Off-target analysis of in-house made Trem2 R47H knock-in mice. a Sanger-sequencing chromatograms of the Trem2 on-target site and the six putative off target sites of animal Trem2 R47H ki ID-7. Mixed peaks in the Trem2 locus show the correct R47H substitution (CGC > CAC) and the three silent mutations for genotyping purposes. Mixed peaks in traces of site #2 reveal a Δ10-Indel mutation at the putative cut site, indicating a true off target event. Underlined: Protospacer; arrow head: putative cut site; green letters: PAM site on shown strand; red letters: PAM site on complementary strand; yellow: Δ10-Indel mutation. b Sanger sequencing results of Trem2 R47H positive off-springs of male ID-7, which was crossed with a C57BL/6 N female. The Δ10-Indel allele was inherited to animals ID-7-3 und ID-7-12 that were excluded from any further breedings and experiments. (PDF 201 kb)

Published
2018
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233. Bevacizumab reduces toxicity of reirradiation in recurrent high-grade glioma

Author

Fleischmann, Daniel Felix, primary, Jenn, Johanna, additional, Corradini, Stefanie, additional, Ruf, Viktoria, additional, Herms, Jochen, additional, Forbrig, Robert, additional, Unterrainer, Marcus, additional, Thon, Niklas, additional, Kreth, Friedrich Wilhelm, additional, Belka, Claus, additional, and Niyazi, Maximilian, additional

Published
2019
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234. Early defects in translation elongation factor 1α levels at excitatory synapses in α-synucleinopathy

Author

Blumenstock, Sonja, primary, Angelo, Maria Florencia, additional, Peters, Finn, additional, Dorostkar, Mario M., additional, Ruf, Viktoria C., additional, Luckner, Manja, additional, Crux, Sophie, additional, Slapakova, Lenka, additional, Arzberger, Thomas, additional, Claverol, Stéphane, additional, Herzog, Etienne, additional, and Herms, Jochen, additional

Published
2019
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235. Non-invasive prediction of IDH-wildtype genotype in gliomas using dynamic 18F-FET PET

Author

Vettermann, Franziska, primary, Suchorska, Bogdana, additional, Unterrainer, Marcus, additional, Nelwan, Debie, additional, Forbrig, Robert, additional, Ruf, Viktoria, additional, Wenter, Vera, additional, Kreth, Friedrich-Wilhelm, additional, Herms, Jochen, additional, Bartenstein, Peter, additional, Tonn, Jörg-Christian, additional, and Albert, Nathalie L., additional

Published
2019
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236. Late-stage Anle138b treatment ameliorates tau pathology and metabolic decline in a mouse model of human Alzheimer’s disease tau

Author

Brendel, Matthias, primary, Deussing, Maximilian, additional, Blume, Tanja, additional, Kaiser, Lena, additional, Probst, Federico, additional, Overhoff, Felix, additional, Peters, Finn, additional, von Ungern-Sternberg, Barbara, additional, Ryazanov, Sergey, additional, Leonov, Andrei, additional, Griesinger, Christian, additional, Zwergal, Andreas, additional, Levin, Johannes, additional, Bartenstein, Peter, additional, Yakushev, Igor, additional, Cumming, Paul, additional, Boening, Guido, additional, Ziegler, Sibylle, additional, Herms, Jochen, additional, Giese, Armin, additional, and Rominger, Axel, additional

Published
2019
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237. The neuropathology of fatal encephalomyelitis in human Borna virus infection

Author

Liesche, Friederike, primary, Ruf, Viktoria, additional, Zoubaa, Saida, additional, Kaletka, Gwendolyn, additional, Rosati, Marco, additional, Rubbenstroth, Dennis, additional, Herden, Christiane, additional, Goehring, Lutz, additional, Wunderlich, Silke, additional, Wachter, Miguel Frederic, additional, Rieder, Georg, additional, Lichtmannegger, Ines, additional, Permanetter, Willibald, additional, Heckmann, Josef G., additional, Angstwurm, Klemens, additional, Neumann, Bernhard, additional, Märkl, Bruno, additional, Haschka, Stefan, additional, Niller, Hans-Helmut, additional, Schmidt, Barbara, additional, Jantsch, Jonathan, additional, Brochhausen, Christoph, additional, Schlottau, Kore, additional, Ebinger, Arnt, additional, Hemmer, Bernhard, additional, Riemenschneider, Markus J., additional, Herms, Jochen, additional, Beer, Martin, additional, Matiasek, Kaspar, additional, and Schlegel, Jürgen, additional

Published
2019
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238. Longitudinal PET Monitoring of Amyloidosis and Microglial Activation in a Second-Generation Amyloid-β Mouse Model

Author

Sacher, Christian, primary, Blume, Tanja, additional, Beyer, Leonie, additional, Peters, Finn, additional, Eckenweber, Florian, additional, Sgobio, Carmelo, additional, Deussing, Maximilian, additional, Albert, Nathalie L., additional, Unterrainer, Marcus, additional, Lindner, Simon, additional, Gildehaus, Franz-Josef, additional, von Ungern-Sternberg, Barbara, additional, Brzak, Irena, additional, Neumann, Ulf, additional, Saito, Takashi, additional, Saido, Takaomi C., additional, Bartenstein, Peter, additional, Rominger, Axel, additional, Herms, Jochen, additional, and Brendel, Matthias, additional

Published
2019
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239. P2-376: 18F-PI2620 TAU-PET IN PROGRESSIVE SUPRANUCLEAR PALSY: A MULTI-CENTER EVALUATION

Author

Brendel, Matthias, primary, Barthel, Henryk, additional, van Eimeren, Thilo, additional, Marek, Ken, additional, Beyer, Leonie, additional, Song, Mengmeng, additional, Palleis, Carla, additional, Respondek, Gesine, additional, Sauerbeck, Julia, additional, Hammes, Jochen, additional, Barbe, Michael, additional, Onur, Oezguer A., additional, Jessen, Frank, additional, Saur, Dorothee, additional, Schroeter, Matthias L., additional, Rumpf, Jost-Julian, additional, Rullmann, Michael, additional, Schildan, Andreas, additional, Patt, Marianne, additional, Barret, Oliver, additional, Madonia, Jennifer, additional, Russell, David, additional, Stephens, Andrew Wills, additional, Roeber, Sigrun, additional, Herms, Jochen, additional, Boetzel, Kai, additional, Levin, Johannes, additional, Classen, Joseph, additional, Höglinger, Günter, additional, Bartenstein, Peter, additional, Drzezga, Alexander, additional, Seibyl, John, additional, and Sabri, Osama, additional

Published
2019
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240. IC‐P‐161: 18F‐PI2620 TAU‐PET IN PROGRESSIVE SUPRANUCLEAR PALSY: A MULTI‐CENTER EVALUATION

Author

Brendel, Matthias, primary, Barthel, Henryk, additional, van Eimeren, Thilo, additional, Marek, Ken, additional, Beyer, Leonie, additional, Song, Mengmeng, additional, Palleis, Carla, additional, Respondek, Gesine, additional, Sauerbeck, Julia, additional, Hammes, Jochen, additional, Barbe, Michael, additional, Onur, Oezguer A., additional, Jessen, Frank, additional, Saur, Dorothee, additional, Schroeter, Matthias L., additional, Rumpf, Jost-Julian, additional, Rullmann, Michael, additional, Schildan, Andreas, additional, Patt, Marianne, additional, Barret, Oliver, additional, Madonia, Jennifer, additional, Russell, David, additional, Stephens, Andrew Wills, additional, Roeber, Sigrun, additional, Herms, Jochen, additional, Boetzel, Kai, additional, Levin, Johannes, additional, Classen, Joseph, additional, Höglinger, Günter, additional, Bartenstein, Peter, additional, Drzezga, Alexander, additional, Seibyl, John, additional, and Sabri, Osama, additional

Published
2019
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244. Genome-wide analyses as part of the international FTLD-TDP whole-genome sequencing consortium reveals novel disease risk factors and increases support for immune dysfunction in FTLD

Author

Pottier, Cyril, primary, Ren, Yingxue, additional, Perkerson, Ralph B., additional, Baker, Matt, additional, Jenkins, Gregory D., additional, van Blitterswijk, Marka, additional, DeJesus-Hernandez, Mariely, additional, van Rooij, Jeroen G. J., additional, Murray, Melissa E., additional, Christopher, Elizabeth, additional, McDonnell, Shannon K., additional, Fogarty, Zachary, additional, Batzler, Anthony, additional, Tian, Shulan, additional, Vicente, Cristina T., additional, Matchett, Billie, additional, Karydas, Anna M., additional, Hsiung, Ging-Yuek Robin, additional, Seelaar, Harro, additional, Mol, Merel O., additional, Finger, Elizabeth C., additional, Graff, Caroline, additional, Öijerstedt, Linn, additional, Neumann, Manuela, additional, Heutink, Peter, additional, Synofzik, Matthis, additional, Wilke, Carlo, additional, Prudlo, Johannes, additional, Rizzu, Patrizia, additional, Simon-Sanchez, Javier, additional, Edbauer, Dieter, additional, Roeber, Sigrun, additional, Diehl-Schmid, Janine, additional, Evers, Bret M., additional, King, Andrew, additional, Mesulam, M. Marsel, additional, Weintraub, Sandra, additional, Geula, Changiz, additional, Bieniek, Kevin F., additional, Petrucelli, Leonard, additional, Ahern, Geoffrey L., additional, Reiman, Eric M., additional, Woodruff, Bryan K., additional, Caselli, Richard J., additional, Huey, Edward D., additional, Farlow, Martin R., additional, Grafman, Jordan, additional, Mead, Simon, additional, Grinberg, Lea T., additional, Spina, Salvatore, additional, Grossman, Murray, additional, Irwin, David J., additional, Lee, Edward B., additional, Suh, EunRan, additional, Snowden, Julie, additional, Mann, David, additional, Ertekin-Taner, Nilufer, additional, Uitti, Ryan J., additional, Wszolek, Zbigniew K., additional, Josephs, Keith A., additional, Parisi, Joseph E., additional, Knopman, David S., additional, Petersen, Ronald C., additional, Hodges, John R., additional, Piguet, Olivier, additional, Geier, Ethan G., additional, Yokoyama, Jennifer S., additional, Rissman, Robert A., additional, Rogaeva, Ekaterina, additional, Keith, Julia, additional, Zinman, Lorne, additional, Tartaglia, Maria Carmela, additional, Cairns, Nigel J., additional, Cruchaga, Carlos, additional, Ghetti, Bernardino, additional, Kofler, Julia, additional, Lopez, Oscar L., additional, Beach, Thomas G., additional, Arzberger, Thomas, additional, Herms, Jochen, additional, Honig, Lawrence S., additional, Vonsattel, Jean Paul, additional, Halliday, Glenda M., additional, Kwok, John B., additional, White, Charles L., additional, Gearing, Marla, additional, Glass, Jonathan, additional, Rollinson, Sara, additional, Pickering-Brown, Stuart, additional, Rohrer, Jonathan D., additional, Trojanowski, John Q., additional, Van Deerlin, Vivianna, additional, Bigio, Eileen H., additional, Troakes, Claire, additional, Al-Sarraj, Safa, additional, Asmann, Yan, additional, Miller, Bruce L., additional, Graff-Radford, Neill R., additional, Boeve, Bradley F., additional, Seeley, William W., additional, Mackenzie, Ian R. A., additional, van Swieten, John C., additional, Dickson, Dennis W., additional, Biernacka, Joanna M., additional, and Rademakers, Rosa, additional

Published
2019
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245. Publisher Correction: ApoE attenuates unresolvable inflammation by complex formation with activated C1q

Author

Yin, Changjun, primary, Ackermann, Susanne, additional, Ma, Zhe, additional, Mohanta, Sarajo K., additional, Zhang, Chuankai, additional, Li, Yuanfang, additional, Nietzsche, Sandor, additional, Westermann, Martin, additional, Peng, Li, additional, Hu, Desheng, additional, Bontha, Sai Vineela, additional, Srikakulapu, Prasad, additional, Beer, Michael, additional, Megens, Remco T. A., additional, Steffens, Sabine, additional, Hildner, Markus, additional, Halder, Luke D., additional, Eckstein, Hans-Henning, additional, Pelisek, Jaroslav, additional, Herms, Jochen, additional, Roeber, Sigrun, additional, Arzberger, Thomas, additional, Borodovsky, Anna, additional, Habenicht, Livia, additional, Binder, Christoph J., additional, Weber, Christian, additional, Zipfel, Peter F., additional, Skerka, Christine, additional, and Habenicht, Andreas J. R., additional

Published
2019
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246. ApoE attenuates unresolvable inflammation by complex formation with activated C1q

Author

Yin, Changjun, primary, Ackermann, Susanne, additional, Ma, Zhe, additional, Mohanta, Sarajo K., additional, Zhang, Chuankai, additional, Li, Yuanfang, additional, Nietzsche, Sandor, additional, Westermann, Martin, additional, Peng, Li, additional, Hu, Desheng, additional, Bontha, Sai Vineela, additional, Srikakulapu, Prasad, additional, Beer, Michael, additional, Megens, Remco T. A., additional, Steffens, Sabine, additional, Hildner, Markus, additional, Halder, Luke D., additional, Eckstein, Hans-Henning, additional, Pelisek, Jaroslav, additional, Herms, Jochen, additional, Roeber, Sigrun, additional, Arzberger, Thomas, additional, Borodovsky, Anna, additional, Habenicht, Livia, additional, Binder, Christoph J., additional, Weber, Christian, additional, Zipfel, Peter F., additional, Skerka, Christine, additional, and Habenicht, Andreas J. R., additional

Published
2019
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247. In vivo Ca 2+ imaging of astrocytic microdomains reveals a critical role of the amyloid precursor protein for mitochondria

Author

Montagna, Elena, primary, Crux, Sophie, additional, Luckner, Manja, additional, Herber, Julia, additional, Colombo, Alessio V., additional, Marinković, Petar, additional, Tahirovic, Sabina, additional, Lichtenthaler, Stefan F., additional, Wanner, Gerhard, additional, Müller, Ulrike C., additional, Sgobio, Carmelo, additional, and Herms, Jochen, additional

Published
2019
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248. Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE

Author

Parhizkar, Samira, primary, Arzberger, Thomas, additional, Brendel, Matthias, additional, Kleinberger, Gernot, additional, Deussing, Maximilian, additional, Focke, Carola, additional, Nuscher, Brigitte, additional, Xiong, Monica, additional, Ghasemigharagoz, Alireza, additional, Katzmarski, Natalie, additional, Krasemann, Susanne, additional, Lichtenthaler, Stefan F., additional, Müller, Stephan A., additional, Colombo, Alessio, additional, Monasor, Laura Sebastian, additional, Tahirovic, Sabina, additional, Herms, Jochen, additional, Willem, Michael, additional, Pettkus, Nadine, additional, Butovsky, Oleg, additional, Bartenstein, Peter, additional, Edbauer, Dieter, additional, Rominger, Axel, additional, Ertürk, Ali, additional, Grathwohl, Stefan A., additional, Neher, Jonas J., additional, Holtzman, David M., additional, Meyer-Luehmann, Melanie, additional, and Haass, Christian, additional

Published
2019
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249. Microglial response to increasing amyloid load saturates with aging: a longitudinal dual tracer in vivo μPET-study

Author

Blume, Tanja, primary, Focke, Carola, additional, Peters, Finn, additional, Deussing, Maximilian, additional, Albert, Nathalie L., additional, Lindner, Simon, additional, Gildehaus, Franz-Josef, additional, von Ungern-Sternberg, Barbara, additional, Ozmen, Laurence, additional, Baumann, Karlheinz, additional, Bartenstein, Peter, additional, Rominger, Axel, additional, Herms, Jochen, additional, and Brendel, Matthias, additional

Published
2018
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