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Article ; Online: Application of real-time quaking-induced conversion in Creutzfeldt-Jakob disease surveillance.

Hermann, Peter / Schmitz, Matthias / Cramm, Maria / Goebel, Stefan / Bunck, Timothy / Schütte-Schmidt, Julia / Schulz-Schaeffer, Walter / Stadelmann, Christine / Matschke, Jakob / Glatzel, Markus / Zerr, Inga

Journal of neurology

2023 Volume 270, Issue 4, Page(s) 2149–2161

Abstract: ... in Creutzfeldt-Jakob disease surveillance to investigate test accuracy, influencing factors, and associations ... characterized patients with sporadic Creutzfeldt-Jakob disease (n = 888) and patients with final diagnosis ... The overall test sensitivity for sporadic Creutzfeldt-Jakob disease was 90% and the specificity 99%. Lower ...

Abstract	Background: Evaluation of the application of CSF real-time quaking-induced conversion in Creutzfeldt-Jakob disease surveillance to investigate test accuracy, influencing factors, and associations with disease incidence. Methods: In a prospective surveillance study, CSF real-time quaking-induced conversion was performed in patients with clinical suspicion of prion disease (2014-2022). Clinically or histochemically characterized patients with sporadic Creutzfeldt-Jakob disease (n = 888) and patients with final diagnosis of non-prion disease (n = 371) were included for accuracy and association studies. Results: The overall test sensitivity for sporadic Creutzfeldt-Jakob disease was 90% and the specificity 99%. Lower sensitivity was associated with early disease stage (p = 0.029) and longer survival (p < 0.001). The frequency of false positives was significantly higher in patients with inflammatory CNS diseases (3.7%) than in other diagnoses (0.4%, p = 0.027). The incidence increased from 1.7 per million person-years (2006-2017) to 2.0 after the test was added to diagnostic the criteria (2018-2021). Conclusion: We validated high diagnostic accuracy of CSF real-time quaking-induced conversion but identified inflammatory brain disease as a potential source of (rare) false-positive results, indicating thorough consideration of this condition in the differential diagnosis of Creutzfeldt-Jakob disease. The surveillance improved after amendment of the diagnostic criteria, whereas the incidence showed no suggestive alterations during the COVID-19 pandemic.
MeSH term(s)	Humans ; Creutzfeldt-Jakob Syndrome/diagnosis ; Creutzfeldt-Jakob Syndrome/epidemiology ; Prospective Studies ; Pandemics ; Sensitivity and Specificity ; COVID-19
Language	English
Publishing date	2023-01-10
Publishing country	Germany
Document type	Journal Article
ZDB-ID	187050-6
ISSN	1432-1459 ; 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
ISSN (online)	1432-1459
ISSN	0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
DOI	10.1007/s00415-022-11549-2
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Article ; Online: (with research data) Validation and utilization of amended diagnostic criteria in Creutzfeldt-Jakob disease surveillance.

Hermann, Peter / Laux, Mareike / Glatzel, Markus / Matschke, Jakob / Knipper, Tobias / Goebel, Stefan / Treig, Johannes / Schulz-Schaeffer, Walter / Cramm, Maria / Schmitz, Matthias / Zerr, Inga

Neurology

2018 Volume 91, Issue 4, Page(s) e331–e338

Abstract: ... Creutzfeldt-Jakob disease (sCJD) including real-time quaking-induced conversion (RT-QuIC) and to observe its use in CJD ...

Abstract	Objective: To validate an amended protocol for clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) including real-time quaking-induced conversion (RT-QuIC) and to observe its use in CJD surveillance. Methods: In the framework of a prospective epidemiologic study, all neuropathologically confirmed cases with sCJD who received CSF RT-QuIC analysis during diagnostic workup (n = 65) and a control group of individuals without CJD (n = 118) were selected to investigate the accuracy of an amended diagnostic protocol. The patients had been referred to the German National Reference Center for Transmissible Spongiform Encephalopathies. The influence of the amended protocol on incidence figures was evaluated in the context of 3 years of surveillance activity (screened cases using 14-3-3 test n = 18,789, highly suspicious cases of CJD n = 704). Annual incidences were calculated with current criteria and the amended protocol. Results: The amended protocol showed a sensitivity of 97% and a specificity of 99%. When it was applied to all suspected cases who were referred to the reference center, the assessed incidence of CJD increased from 1.7 to 2.2 per million in 2016. Conclusion: CJD surveillance remains challenging because information from external health care institutions can be limited. RT-QuIC shows excellent diagnostic accuracy when applied in the clinical setting to symptomatic patients. Data for RT-QuIC alone when applied as a general screening test are not available yet. We propose an amended research protocol that improves early and accurate clinical diagnosis of sCJD during surveillance activities. The use of this protocol will probably lead to a significant increase of the incidence rate. Classification of evidence: This study provides Class III evidence that for patients with suspected sCJD, criteria for clinical diagnosis plus the CSF RT-QuIC accurately identifies patients with sCJD (sensitivity 97%, specificity 99%).
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Brain/diagnostic imaging ; Cohort Studies ; Creutzfeldt-Jakob Syndrome/diagnostic imaging ; Creutzfeldt-Jakob Syndrome/epidemiology ; Female ; Germany/epidemiology ; Humans ; Magnetic Resonance Imaging/standards ; Male ; Middle Aged ; Population Surveillance/methods ; Prospective Studies ; Reproducibility of Results ; Young Adult
Language	English
Publishing date	2018-06-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000005860
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Article ; Online: Distinct microglia profile in Creutzfeldt-Jakob disease and Alzheimer's disease is independent of disease kinetics.

Krbot, Katarina / Hermann, Peter / Skorić, Magdalena Krbot / Zerr, Inga / Sepulveda-Falla, Diego / Goebel, Stefan / Matschke, Jakob / Krasemann, Susanne / Glatzel, Markus

Neuropathology : official journal of the Japanese Society of Neuropathology

2018 Volume 38, Issue 6, Page(s) 591–600

Abstract: ... Creutzfeldt-Jakob disease (sCJD) patients show more pronounced microglial activation than Alzheimer's disease (AD) patients ...

Abstract	Activated microglia represent a common pathological feature of neurodegenerative diseases. Sporadic Creutzfeldt-Jakob disease (sCJD) patients show more pronounced microglial activation than Alzheimer's disease (AD) patients. Whether these differences are due to differences in disease kinetics or represent disease-specific changes is unknown. We investigated microglial phenotypes in brains of rapidly progressive AD (rpAD) and sCJD patients matched for clinical presentation, including disease duration. We immunostained the frontal cortex, basal ganglia and cerebellum in 16 patients with rpAD and sCJD using antibodies against markers of microglia and recruited monocytes (ionized calcium-binding adaptor molecule 1, human leukocyte antigen DPQR, Cluster of Differentiation 68), an antibody unique to brain-resident microglia (transmembrane protein 119 (TMEM119)), in addition to antibodies against a marker of astrocytes (glial fibrillary acidic protein), amyloid-β (Aβ) and pathological prion protein. rpAD patients showed a distinct microglial phenotype with a high abundance of TMEM119-positive microglia in all investigated regions. Presence of Aβ deposits seen in a sCJD patient with concomitant deposition of Aβ led to increase of TMEM119-positive microglia. Our data suggest that in rpAD, activation of brain-resident microglia significantly contributes to microgliosis, whereas in sCJD the TMEM119 signature of resident microglial cells is barely detectable. This is irrespective of disease duration and may indicate disease-specific microglial reaction.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/immunology ; Alzheimer Disease/pathology ; Creutzfeldt-Jakob Syndrome/immunology ; Creutzfeldt-Jakob Syndrome/pathology ; Female ; Humans ; Male ; Microglia/immunology ; Microglia/pathology ; Middle Aged
Language	English
Publishing date	2018-10-15
Publishing country	Australia
Document type	Journal Article
ZDB-ID	1483794-8
ISSN	1440-1789 ; 0919-6544
ISSN (online)	1440-1789
ISSN	0919-6544
DOI	10.1111/neup.12517
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Article: No reactivation of JCV and CMV infections in the temporal cortex and cerebellum of sporadic Creutzfeldt-Jakob disease patients.

Löffler, Judith / Krasemann, Susanne / Zerr, Inga / Matschke, Jakob / Glatzel, Markus

American journal of neurodegenerative disease

2014 Volume 3, Issue 3, Page(s) 152–157

Abstract: Sporadic Creutzfeldt-Jakob disease (sCJD) is characterized by great phenotypic variability ...

Abstract	Sporadic Creutzfeldt-Jakob disease (sCJD) is characterized by great phenotypic variability regarding clinical course and neuropathology. The most prominent disease modifiers are a polymorphism in Codon 129 of the prion protein gene and conformational variations of the misfolded prion protein. The cellular form of the prion protein restricts replication of viruses and may be involved in viral host defense, and viral infections influence the presentation and neuropathology in prion diseased mice. We investigated the occurrence of reactivated persistent viral infections of the brain in brain tissue samples of 25 sCJD patients. No evidence of reactivated JCV and CMV infections could be detected. This suggests that JCV and CMV infections are not reactivated as consequence of prion disease and do not act as disease modifiers in sCJD.
Language	English
Publishing date	2014-12-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2695563-5
ISSN	2165-591X
ISSN	2165-591X
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Article ; Online: Association between deposition of beta-amyloid and pathological prion protein in sporadic Creutzfeldt-Jakob disease.

Debatin, Laura / Streffer, Johannes / Geissen, Markus / Matschke, Jakob / Aguzzi, Adriano / Glatzel, Markus

Neuro-degenerative diseases

2008 Volume 5, Issue 6, Page(s) 347–354

Abstract: Background: Alzheimer's disease (AD) and prion diseases such as sporadic Creutzfeldt-Jakob ...

Abstract	Background: Alzheimer's disease (AD) and prion diseases such as sporadic Creutzfeldt-Jakob disease (sCJD) share common features concerning their molecular pathogenesis and neuropathological presentation and the coexistence of AD and CJD in patients suggest an association between the deposition of the proteolytically processed form of the amyloid precursor protein, beta-amyloid (Abeta), which deposits in AD, and the abnormal form of the prion protein, PrP(Sc), which deposits in sCJD. Methods: We have characterized sCJD patients (n = 14), AD patients (n = 5) and nondemented controls (n = 5) with respect to the deposition of PrP(Sc) and Abeta morphologically, biochemically and genetically and correlated these findings to clinical data. Results: sCJD-diseased individuals with abundant deposits of Abeta present with a specific clinicopathological profile, defined by higher age at disease onset, long disease duration, a genetic profile and only minimal amounts of PrP(Sc) in the cerebellum. Conclusion: The co-occurrence of pathological changes typical for sCJD and AD in combination with the inverse association between accumulation of Abeta and PrP(Sc) in a subgroup of sCJD patients is indicative of common pathways involved in the generation or clearance of Abeta and PrP(Sc) in a subgroup of sCJD patients.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/analysis ; Amyloid beta-Protein Precursor/analysis ; Amyloid beta-Protein Precursor/genetics ; Blotting, Western ; Brain Chemistry ; Creutzfeldt-Jakob Syndrome/genetics ; Creutzfeldt-Jakob Syndrome/metabolism ; Creutzfeldt-Jakob Syndrome/pathology ; Enzyme-Linked Immunosorbent Assay ; Female ; Frontal Lobe/chemistry ; Frontal Lobe/pathology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Peptide Fragments/analysis ; Polymerase Chain Reaction ; PrPSc Proteins/analysis ; Presenilin-1/analysis ; Presenilin-1/genetics ; Presenilin-2/analysis ; Presenilin-2/genetics ; Prion Proteins ; Prions/analysis ; Prions/genetics ; Protease Nexins ; Receptors, Cell Surface/analysis ; Receptors, Cell Surface/genetics
Chemical Substances	Amyloid beta-Peptides ; Amyloid beta-Protein Precursor ; PRNP protein, human ; PSEN1 protein, human ; PSEN2 protein, human ; Peptide Fragments ; PrPSc Proteins ; Presenilin-1 ; Presenilin-2 ; Prion Proteins ; Prions ; Protease Nexins ; Receptors, Cell Surface ; amyloid beta-protein (1-42)
Language	English
Publishing date	2008
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2143569-8
ISSN	1660-2862 ; 1660-2854
ISSN (online)	1660-2862
ISSN	1660-2854
DOI	10.1159/000121389
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Article: Association between Deposition of Beta-Amyloid and Pathological Prion Protein in Sporadic Creutzfeldt-Jakob Disease

Debatin, Laura / Streffer, Johannes / Geissen, Markus / Matschke, Jakob / Aguzzi, Adriano / Glatzel, Markus

Neurodegenerative Diseases

2008 Volume 5, Issue 6, Page(s) 347–354

Abstract: Background: Alzheimer’s disease (AD) and prion diseases such as sporadic Creutzfeldt-Jakob ...

Institution	Institute of Neuropathology, and Division of Psychiatry Research, University Hospital Zurich, Zurich, Switzerland Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Abstract	Background: Alzheimer’s disease (AD) and prion diseases such as sporadic Creutzfeldt-Jakob disease (sCJD) share common features concerning their molecular pathogenesis and neuropathological presentation and the coexistence of AD and CJD in patients suggest an association between the deposition of the proteolytically processed form of the amyloid precursor protein, β-amyloid (Aβ), which deposits in AD, and the abnormal form of the prion protein, PrPSc, which deposits in sCJD. Methods: We have characterized sCJD patients (n = 14), AD patients (n = 5) and nondemented controls (n = 5) with respect to the deposition of PrPSc and Aβ morphologically, biochemically and genetically and correlated these findings to clinical data. Results: sCJD-diseased individuals with abundant deposits of Aβ present with a specific clinicopathological profile, defined by higher age at disease onset, long disease duration, a genetic profile and only minimal amounts of PrPSc in the cerebellum. Conclusion: The co-occurrence of pathological changes typical for sCJD and AD in combination with the inverse association between accumulation of Aβ and PrPSc in a subgroup of sCJD patients is indicative of common pathways involved in the generation or clearance of Aβ and PrPSc in a subgroup of sCJD patients.
Keywords	Sporadic Creutzfeldt-Jakob disease ; Alzheimer’s disease ; Deposition of β-amyloid ; Prion protein
Language	English
Publishing date	2008-03-18
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Original Paper
ZDB-ID	2143569-8
ISSN	1660-2862 ; 1660-2854
ISSN (online)	1660-2862
ISSN	1660-2854
DOI	10.1159/000121389
Database	Karger publisher's database

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Zs.A 5918: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 567: Show issues

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Book ; Thesis: Die Magnetstimulation des Nervensystems

Matschke, Jakob

Untersuchungen an gesunden Probanden ; Normwerte unter Berücksichtigung der Literatur der Jahre 1987 - 1994

1996

Author's details	vorgelegt von: Jakob Matschke
Language	German
Size	101 S. : graph. Darst.
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Bonn, Univ., Diss., 1996
HBZ-ID	HT007169167
Database	Catalogue ZB MED Medicine, Health

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96 D 2525	order for loan	Magazin

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Article: Targeting AKT-Dependent Regulation of Antioxidant Defense Sensitizes AKT-E17K Expressing Cancer Cells to Ionizing Radiation.

Goetting, Isabell / Larafa, Safa / Eul, Katharina / Kunin, Mikhail / Jakob, Burkhard / Matschke, Johann / Jendrossek, Verena

Frontiers in oncology

2022 Volume 12, Page(s) 920017

Abstract: Aberrant activation of the phosphatidyl-inositol-3-kinase/protein kinase B (AKT) pathway has clinical relevance to radiation resistance, but the underlying mechanisms are incompletely understood. Protection against reactive oxygen species (ROS) plays an ... ...

Abstract	Aberrant activation of the phosphatidyl-inositol-3-kinase/protein kinase B (AKT) pathway has clinical relevance to radiation resistance, but the underlying mechanisms are incompletely understood. Protection against reactive oxygen species (ROS) plays an emerging role in the regulation of cell survival upon irradiation. AKT-dependent signaling participates in the regulation of cellular antioxidant defense. Here, we were interested to explore a yet unknown role of aberrant activation of AKT in regulating antioxidant defense in response to IR and associated radiation resistance. We combined genetic and pharmacologic approaches to study how aberrant activation of AKT impacts cell metabolism, antioxidant defense, and radiosensitivity. Therefore, we used TRAMPC1 (TrC1) prostate cancer cells overexpressing the clinically relevant AKT-variant AKT-E17K with increased AKT activity or wildtype AKT (AKT-WT) and analyzed the consequences of direct AKT inhibition (MK2206) and inhibition of AKT-dependent metabolic enzymes on the levels of cellular ROS, antioxidant capacity, metabolic state, short-term and long-term survival without and with irradiation. TrC1 cells expressing the clinically relevant AKT1-E17K variant were characterized by improved antioxidant defense compared to TrC1 AKT-WT cells and this was associated with increased radiation resistance. The underlying mechanisms involved AKT-dependent direct and indirect regulation of cellular levels of reduced glutathione (GSH). Pharmacologic inhibition of specific AKT-dependent metabolic enzymes supporting defense against oxidative stress, e.g., inhibition of glutathione synthase and glutathione reductase, improved eradication of clonogenic tumor cells, particularly of TrC1 cells overexpressing AKT-E17K. We conclude that improved capacity of TrC1 AKT-E17K cells to balance antioxidant defense with provision of energy and other metabolites upon irradiation compared to TrC1 AKT-WT cells contributes to their increased radiation resistance. Our findings on the importance of glutathione
Language	English
Publishing date	2022-07-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.920017
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Article: Cavernous Malformations and Hemangioblastomas of the Spinal Cord Show Distinct Differences in Clinical Course - A Retrospective Single-Center Analysis of 112 Patients.

Pantel, Tobias / Mende, Klaus Christian / Mohme, Theresa / Mohme, Malte / Viezens, Lennart / Matschke, Jakob / Westphal, Manfred / Eicker, Sven Oliver

Global spine journal

2023 , Page(s) 21925682231214363

Abstract: Study design: Retrospective cohort study.: Objective: Cavernous malformations (CMs) and hemangioblastomas (HBs) of the spinal cord exhibit distinct differences in histopathology but similarities in the neurological course. The aim of our study was to ...

Abstract	Study design: Retrospective cohort study. Objective: Cavernous malformations (CMs) and hemangioblastomas (HBs) of the spinal cord exhibit distinct differences in histopathology but similarities in the neurological course. The aim of our study was to analyze the clinical differences between the vascular pathologies and a benign tumor of the spinal cord in a perioperative situation. Methods: We performed a retrospective analysis of patients who had undergone surgery for lesions in the spinal cord between 1984 and 2015. Patients were screened for CMs and HBs as the primary inclusion criteria. General patient information, surgical data, and disease-specific data were collected from the records. Cooper-Epstein scores for clinical symptoms were evaluated preoperatively, at discharge, and at the 6-month follow-up. Results: A total of 112 patients were included, of which 46 had been diagnosed with CMs and 66 with HBs. Patients with CMs often demonstrated more preoperative neurological deterioration compared to those with HBs ( Conclusion: CMs and HBs of the spinal cord have similarities but also exhibit significant differences in neurological presentation and perioperative course. Surgical therapy is the treatment of choice for symptomatic lesions, and complete surgical resection is possible in the majority of cases for both entities. Neurologic outcomes are usually favorable, although patients with HBs retain neurologic deficits more often.
Language	English
Publishing date	2023-11-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2648287-3
ISSN	2192-5690 ; 2192-5682
ISSN (online)	2192-5690
ISSN	2192-5682
DOI	10.1177/21925682231214363
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Article ; Online: Neuropathology associated with SARS-CoV-2 infection.

Glatzel, Markus / Hagel, Christian / Matschke, Jakob / Sperhake, Jan / Deigendesch, Nikolaus / Tzankov, Alexandar / Frank, Stephan

Lancet (London, England)

2021 Volume 397, Issue 10271, Page(s) 276

MeSH term(s)	Brain ; COVID-19 ; Humans ; Nervous System Diseases ; SARS-CoV-2
Language	English
Publishing date	2021-01-23
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	3306-6
ISSN	1474-547X ; 0023-7507 ; 0140-6736
ISSN (online)	1474-547X
ISSN	0023-7507 ; 0140-6736
DOI	10.1016/S0140-6736(21)00098-2
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Zs.MG 94: Show issues

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