المؤلفون: Annemieke J.M. Rozemuller, Jeroen J.M. Hoozemans, Tjado H. J. Morrema, Jurre den Haan, Femke H. Bouwman

المساهمون: Neurology, Amsterdam Neuroscience - Neurodegeneration, NCA - neurodegeneration, Pathology

المصدر: Acta Neuropathologica Communications, Vol 6, Iss 1, Pp 1-12 (2018)
Acta Neuropathologica Communications
den Haan, J, Morrema, T H J, Rozemuller, A J, Bouwman, F H & Hoozemans, J J M 2018, ' Different curcumin forms selectively bind fibrillar amyloid beta in post mortem Alzheimer's disease brains : Implications for in-vivo diagnostics ', Acta Neuropathologica Communinications, vol. 6, no. 1, pp. 75 . https://doi.org/10.1186/s40478-018-0577-2Test
Acta Neuropathologica Communinications, 6(1). BioMed Central

مصطلحات موضوعية: 0301 basic medicine, Male, Pathology, Plaque, Amyloid, Protein aggregation, lcsh:RC346-429, chemistry.chemical_compound, 0302 clinical medicine, Aged, 80 and over, biology, Neurodegeneration, Anti-Inflammatory Agents, Non-Steroidal, Brain, Neurofibrillary Tangles, Frontotemporal lobar degeneration, Middle Aged, Immunohistochemistry, DNA-Binding Proteins, Tauopathies, Female, Cerebral amyloid angiopathy, Tauopathy, Autopsy, Amyloid-beta, Alzheimer’s disease, Protein Binding, medicine.medical_specialty, Curcumin, Amyloid beta, tau Proteins, Cerebral amyloid angiopathy (CAA), Pathology and Forensic Medicine, 03 medical and health sciences, Cellular and Molecular Neuroscience, Alzheimer Disease, mental disorders, medicine, Humans, lcsh:Neurology. Diseases of the nervous system, Aged, Retrospective Studies, Amyloid beta-Peptides, Dementia with Lewy bodies, Research, Biomarker, medicine.disease, Cerebral Amyloid Angiopathy, 030104 developmental biology, chemistry, biology.protein, Neurology (clinical), Frontotemporal Lobar Degeneration, 030217 neurology & neurosurgery

الوصف: The combined fluorescent and Aβ-binding properties of the dietary spice curcumin could yield diagnostic purpose in the search for a non-invasive Aβ-biomarker for Alzheimer’s disease (AD). However, evidence on the binding properties of curcumin, its conjugates and clinically used bio-available formulations to AD neuropathological hallmarks is scarce. We therefore assessed the binding properties of different curcumin forms to different neuropathological deposits in post-mortem brain tissue of cases with AD, other neurodegenerative diseases, and controls. Post mortem brain tissue was histochemically assessed for the binding of curcumin, its isoforms, conjugates and bio-available forms and compared to routinely used staining methods. For this study we included brains of early onset AD, late onset AD, primary age-related tauopathy (PART), cerebral amyloid angiopathy (CAA), frontotemporal lobar degeneration (FTLD) with tau or TAR DNA-binding protein 43 (TDP-43) inclusions, dementia with Lewy bodies (DLB), Parkinson’s disease (PD) and control cases without brain pathology. We found that curcumin binds to fibrillar amyloid beta (Aβ) in plaques and CAA. It does not specifically bind to inclusions of protein aggregates in FTLD-tau cases, TDP-43, or Lewy bodies. Curcumin isoforms, conjugates and bio-available forms show affinity for the same Aβ structures. Curcumin staining overlaps with immunohistochemical detection of Aβ in fibrillar plaques and CAA, and to a lesser extent cored plaques. A weak staining of neurofibrillary tangles was observed, while other structures immunopositive for phosphorylated tau remained negative. In conclusion, curcumin, its isoforms, conjugates and bio-available forms selectively bind fibrillar Aβ in plaques and CAA in post mortem AD brain tissue. Curcumin, being a food additive with fluorescent properties, is therefore an interesting candidate for in-vivo diagnostics in AD, for example in retinal fluorescent imaging.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9ed4d6594a8ef93e3e5b1571bb54b40fTest
http://link.springer.com/article/10.1186/s40478-018-0577-2Test

المؤلفون: Jeroen J.M. Hoozemans, null Netherlands Brain Bank, Marc Hulsman, Philip Scheltens, Annemieke J.M. Rozemuller, Nina Beker, August B. Smit, Henne Holstege, Andrea B. Ganz, Sietske A.M. Sikkes

المساهمون: Netherlands Institute for Neuroscience (NIN), Molecular and Cellular Neurobiology, Amsterdam Neuroscience - Neurodegeneration, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Center for Neurogenomics and Cognitive Research, Pathology, Neurology, Human genetics

المصدر: Acta Neuropathologica Communications, Vol 6, Iss 1, Pp 1-13 (2018)
Acta Neuropathologica Communications
Acta neuropathologica communications, 6(1):64. BioMed Central
Acta Neuropathologica Communications, 6(1):64, 1-13. BioMed Central
Ganz, A B, Beker, N, Hulsman, M, Sikkes, S, Netherlands Brain Bank,, Scheltens, P, Smit, A B, Rozemuller, A J M, Hoozemans, J J M & Holstege, H 2018, ' Neuropathology and cognitive performance in self-reported cognitively healthy centenarians ', Acta Neuropathologica Communinications, vol. 6, no. 1, pp. 64 . https://doi.org/10.1186/s40478-018-0558-5Test, https://doi.org/10.1186/s40478-018-0558-5Test
Ganz, A B, Beker, N, Hulsman, M, Sikkes, S A M, Scheltens, P, Smit, A B, Rozemuller, A J M, Hoozemans, J J M & Holstege, H 2018, ' Neuropathology and cognitive performance in self-reported cognitively healthy centenarians ', Acta Neuropathologica Communications, vol. 6, no. 1, 64, pp. 1-13 . https://doi.org/10.1186/s40478-018-0558-5Test
Acta Neuropathologica Communinications, 6(1). BioMed Central

مصطلحات موضوعية: 0301 basic medicine, Male, Aging, Neurology, Disease, Neuropsychological Tests, lcsh:RC346-429, Cohort Studies, 0302 clinical medicine, 100-plus Study, Neuropathology, Aged, 80 and over, Brain, Cognitively healthy centenarians, Magnetic Resonance Imaging, Cognitive test, DNA-Binding Proteins, Healthy aging, Casein Kinase Idelta, Cohort, alpha-Synuclein, Female, Cerebral amyloid angiopathy, Autopsy, Alzheimer’s disease, Clinical psychology, medicine.medical_specialty, tau Proteins, Pathology and Forensic Medicine, 03 medical and health sciences, Cellular and Molecular Neuroscience, SDG 3 - Good Health and Well-being, Journal Article, medicine, Humans, Cognitive Dysfunction, Effects of sleep deprivation on cognitive performance, lcsh:Neurology. Diseases of the nervous system, Amyloid beta-Peptides, Lewy body, business.industry, Research, medicine.disease, Clinicopathological correlation, 030104 developmental biology, Positron-Emission Tomography, Neurology (clinical), Self Report, business, Mental Status Schedule, 030217 neurology & neurosurgery

الوصف: With aging, the incidence of neuropathological hallmarks of neurodegenerative diseases increases in the brains of cognitively healthy individuals. It is currently unclear to what extent these hallmarks associate with symptoms of disease at extreme ages. Forty centenarians from the 100-plus Study cohort donated their brain. Centenarians self-reported to be cognitively healthy at baseline, which was confirmed by a proxy. Objective ante-mortem measurements of cognitive performance were associated with the prevalence, distribution and quantity of age- and AD-related neuropathological hallmarks. Despite self-reported cognitive health, objective neuropsychological testing suggested varying levels of ante-mortem cognitive functioning. Post-mortem, we found that neuropathological hallmarks related to age and neurodegenerative diseases, such as Aβ and Tau pathology, as well as atherosclerosis, were abundantly present in most or all centenarians, whereas Lewy body and pTDP-43 pathology were scarce. We observed that increased pathology loads correlated across pathology subtypes, and an overall trend of higher pathology loads to associate with a lower cognitive test performance. This trend was carried especially by the presence of neurofibrillary tangles (NFTs) and granulovacuolar degeneration (GVD) and to a lesser extent by Aβ-associated pathologies. Cerebral Amyloid Angiopathy (CAA) specifically associated with lower executive functioning in the centenarians. In conclusion, we find that while the centenarians in this cohort escaped or delayed cognitive impairment until extreme ages, their brains reveal varying levels of disease-associated neuropathological hallmarks, some of which associate with cognitive performance. Electronic supplementary material The online version of this article (10.1186/s40478-018-0558-5) contains supplementary material, which is available to authorized users.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5f3c2e50dabb23549aa6e95a63586e54Test
https://research.vu.nl/en/publications/1e0ef5c7-ec70-4d7e-bae8-b3496da2f6c0Test

المؤلفون: Marianne Borgers, Jeroen J.M. Hoozemans, Roosmarijn Janson, Jarek Juraszek, Lore Delbroek, Berdien Siregar, Marc Mercken, Imke Sprengers, Adrian Apetri, Jeroen van Ameijde, Roland Willems, Kristof Van Kolen, Wouter Koudstaal, Koen Dockx, Gabriel Pascual, Tariq Nahar, Hanneke Verveen, Stefan Steinbacher, Rosa Crespo

المساهمون: Pathology, Amsterdam Neuroscience - Neurodegeneration

المصدر: Acta Neuropathologica Communications, Vol 6, Iss 1, Pp 1-14 (2018)
Acta Neuropathologica Communinications, 6(1):59. BioMed Central
Acta Neuropathologica Communications
van Ameijde, J, Crespo, R, Janson, R, Juraszek, J, Siregar, B, Verveen, H, Sprengers, I, Nahar, T, Hoozemans, J J, Steinbacher, S, Willems, R, Delbroek, L, Borgers, M, Dockx, K, van Kolen, K, Mercken, M, Pascual, G, Koudstaal, W & Apetri, A 2018, ' Enhancement of therapeutic potential of a naturally occurring human antibody targeting a phosphorylated Ser 422 containing epitope on pathological tau ', Acta Neuropathologica Communinications, vol. 6, no. 1, 59 . https://doi.org/10.1186/s40478-018-0562-9Test, https://doi.org/10.1186/s40478-018-0562-9Test

مصطلحات موضوعية: Male, Models, Molecular, 0301 basic medicine, Antibody Affinity, Microscopy, Atomic Force, Epitope, lcsh:RC346-429, Epitopes, Mice, 0302 clinical medicine, Serine, Phosphorylation, Aged, 80 and over, biology, Chemistry, Brain, Middle Aged, 3. Good health, Cell biology, Nucleation, Female, Autopsy, Antibody, Genetically modified mouse, Monoclonal antibody, medicine.drug_class, Tau protein, Mutagenesis (molecular biology technique), Mice, Transgenic, tau Proteins, Intervention, Protein Aggregation, Pathological, Antibodies, Pathology and Forensic Medicine, 03 medical and health sciences, Cellular and Molecular Neuroscience, Aggregation, Alzheimer Disease, medicine, Animals, Humans, lcsh:Neurology. Diseases of the nervous system, Aged, Dose-Response Relationship, Drug, Research, Native chemical ligation, In vitro, 030104 developmental biology, Mutagenesis, Mutation, biology.protein, Neurology (clinical), Tau, 030217 neurology & neurosurgery

الوصف: Aggregation of tau protein and spreading of tau aggregates are pivotal pathological processes in a range of neurological disorders. Accumulating evidence suggests that immunotherapy targeting tau may be a viable therapeutic strategy. We have previously described the isolation of antibody CBTAU-22.1 from the memory B-cell repertoire of healthy human donors. CBTAU-22.1 was shown to specifically bind a disease-associated phosphorylated epitope in the C-terminus of tau (Ser422) and to be able to inhibit the spreading of pathological tau aggregates from P301S spinal cord lysates in vitro, albeit with limited potency. Using a combination of rational design and random mutagenesis we have derived a variant antibody with improved affinity while maintaining the specificity of the parental antibody. This affinity improved antibody showed greatly enhanced potency in a cell-based immunodepletion assay using paired helical filaments (PHFs) derived from human Alzheimer’s disease (AD) brain tissue. Moreover, the affinity improved antibody limits the in vitro aggregation propensity of full length tau species specifically phosphorylated at position 422 produced by employing a native chemical ligation approach. Together, these results indicate that in addition to being able to inhibit the spreading of pathological tau aggregates, the matured antibody can potentially also interfere with the nucleation of tau which is believed to be the first step of the pathogenic process. Finally, the functionality in a P301L transgenic mice co-injection model highlights the therapeutic potential of human antibody dmCBTAU-22.1. Electronic supplementary material The online version of this article (10.1186/s40478-018-0562-9) contains supplementary material, which is available to authorized users.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::82ad08e9acdefdbe11f8ec2bf4a53f53Test
http://link.springer.com/article/10.1186/s40478-018-0562-9Test

المؤلفون: Jeroen van Ameijde, Trevin Holland, Hanna Inganäs, Ian A. Wilson, Gabriel Pascual, Hanneke Verveen, Roosmarijn Janson, Donata de Marco, Jeroen J.M. Hoozemans, Esther J. M. Stoop, Stefan Steinbacher, Renske Taggenbrock, Berdien Siregar, Rosa Crespo, Jay Wadia, Wouter Koudstaal, Margot van Winsen, Koen Dockx, Adrian Constantin Apetri, Jaap Goudsmit, Wenli Yu, David Zuijdgeest, Marianne Borgers, Jarek Juraszek, Heng Zhang, Elissa Keogh, Kristof Van Kolen, Kimberley Ummenthum, Martin H. Koldijk, Marc Mercken, Xueyong Zhu, Els C. M. Brinkman-Van der Linden, Michael Mrosek

المساهمون: VU University medical center, Pathology, Amsterdam Neuroscience - Neurodegeneration

المصدر: Acta Neuropathologica Communications, Vol 6, Iss 1, Pp 1-17 (2018)
Apetri, A, Crespo, R, Juraszek, J, Pascual, G, Janson, R, Zhu, X, Zhang, H, Keogh, E, Holland, T, Wadia, J, Verveen, H, Siregar, B, Mrosek, M, Taggenbrock, R, Ameijde, J, Inganäs, H, van Winsen, M, Koldijk, M H, Zuijdgeest, D, Borgers, M, Dockx, K, Stoop, E J M, Yu, W, Brinkman-van der Linden, E C, Ummenthum, K, van Kolen, K, Mercken, M, Steinbacher, S, de Marco, D, Hoozemans, J J, Wilson, I A, Koudstaal, W & Goudsmit, J 2018, ' A common antigenic motif recognized by naturally occurring human V H 5-51/V L 4-1 anti-tau antibodies with distinct functionalities ', Acta Neuropathologica Communinications, vol. 6, no. 1, 43, pp. 43 . https://doi.org/10.1186/s40478-018-0543-zTest, https://doi.org/10.1186/s40478-018-0543-zTest
Acta Neuropathologica Communinications, 6(1):43. BioMed Central

مصطلحات موضوعية: 0301 basic medicine, Monoclonal antibody, medicine.drug_class, Tau protein, Antigenic motif, Epitope, lcsh:RC346-429, Pathology and Forensic Medicine, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Immune system, Antigen, medicine, lcsh:Neurology. Diseases of the nervous system, Microglia, biology, Chemistry, 3. Good health, Cell biology, 030104 developmental biology, medicine.anatomical_structure, biology.protein, Paired helical filaments, Neurology (clinical), Antibody, Alzheimer’s disease, 030217 neurology & neurosurgery

الوصف: Misfolding and aggregation of tau protein are closely associated with the onset and progression of Alzheimer's Disease (AD). By interrogating IgG + memory B cells from asymptomatic donors with tau peptides, we have identified two somatically mutated V H 5-51/V L 4-1 antibodies. One of these, CBTAU-27.1, binds to the aggregation motif in the R3 repeat domain and blocks the aggregation of tau into paired helical filaments (PHFs) by sequestering monomeric tau. The other, CBTAU-28.1, binds to the N-terminal insert region and inhibits the spreading of tau seeds and mediates the uptake of tau aggregates into microglia by binding PHFs. Crystal structures revealed that the combination of V H 5-51 and V L 4-1 recognizes a common Pro-X n -Lys motif driven by germline-encoded hotspot interactions while the specificity and thereby functionality of the antibodies are defined by the CDR3 regions. Affinity improvement led to improvement in functionality, identifying their epitopes as new targets for therapy and prevention of AD.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c0cc3ef318c798400926689fc83aaa11Test
http://link.springer.com/article/10.1186/s40478-018-0543-zTest

المؤلفون: Saskia M. van der Vies, Jeroen J.M. Hoozemans, Wiesje M. van der Flier, Annemieke J.M. Rozemuller, Andrea F.N. Rosenberger, Philip Scheltens

المساهمون: Neurology, Pathology, NCA - neurodegeneration, Neuroscience Campus Amsterdam - Neurodegeneration, Chemistry and Pharmaceutical Sciences, AIMMS

المصدر: Rosenberger, A, Rozemuller, A J M, van der Flier, W M, Scheltens, P, van der Vies, S M & Hoozemans, J J M 2014, ' Altered distribution of the EphA4 kinase in hippocampal brain tissue of patients with Alzheimer's disease correlates with pathology ', Acta Neuropathologica Communinications, vol. 2, 79 . https://doi.org/10.1186/s40478-014-0079-9Test
Acta Neuropathologica Communinications, 2:79. BioMed Central
Rosenberger, A, Rozemuller, A J M, van der Flier, W M, Scheltens, P, van der Vies, S M & Hoozemans, J J M 2014, ' Altered distribution of the EphA4 kinase in hippocampal brain tissue of patients with Alzheimer's disease correlates with pathology ', Acta Neuropathologica Communications, vol. 2, 79, pp. 1-13 . https://doi.org/10.1186/s40478-014-0079-9Test
Acta Neuropathologica Communications
Acta Neuropathologica Communications, 2:79, 1-13. BioMed Central

مصطلحات موضوعية: Male, Pathology, medicine.medical_specialty, Amyloid beta, Hippocampus, Plaque, Amyloid, tau Proteins, Hippocampal formation, Pathology and Forensic Medicine, Cellular and Molecular Neuroscience, EPH receptor A4, SDG 3 - Good Health and Well-being, Alzheimer Disease, medicine, Humans, Senile plaques, Aged, Aged, 80 and over, biology, business.industry, Research, Neurodegeneration, Receptor, EphA4, Erythropoietin-producing hepatocellular (Eph) receptor, Middle Aged, medicine.disease, Synapse, Immunohistochemistry, EphA4 kinase, biology.protein, Female, Neurology (clinical), Alzheimer's disease, business, Alzheimer’s disease, Neuroscience

الوصف: Synaptic dysfunction occurs early in the progression of Alzheimer’s disease (AD) and correlates with memory decline. There is emerging evidence that deregulation of Erythropoietin-producing hepatocellular (Eph) receptor tyrosine kinases (RTK) signaling contributes to the aberrant synaptic functions associated with neurodegeneration. The Eph receptor A4 is highly expressed in human adult hippocampal brain tissue and was previously linked to cognitive impairment in a transgenic mouse model for AD. Whether EphA4 levels are altered in AD brain remains elusive. Therefore we investigated the protein levels and localization of EphA4 in human hippocampus derived from AD (n = 29) as well as non-demented control cases (n = 19). The total EphA4 protein levels were not changed in AD patients compared to control cases. However, immunohistochemical localization of EphA4 revealed an altered distribution in AD compared to control hippocampus. EphA4 immunoreactivity was observed in plaque-like structures in AD cases. Double-labelling with phosphorylated tau and amyloid beta indicates that EphA4 co-localizes with neuritic plaques in AD. This altered distribution pattern was observed at early stages (Braak stage II) and correlates with the hallmarks of AD pathology suggesting a reduced availability of EphA4 that is likely to contribute to synaptic dysfunction that occurs early in AD. Electronic supplementary material The online version of this article (doi:10.1186/s40478-014-0079-9) contains supplementary material, which is available to authorized users.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8075be916a240fa25ddd69e7d4e57b5bTest