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1.

001-es BibID:BIBFORM069190
Első szerző:Alghamdi, Amani
Cím:Reduction of RPT6/S8 (a Proteasome Component) and Proteasome Activity in the Cortex is Associated with Cognitive Impairment in Lewy Body Dementia / Alghamdi Amani, Vallortigara Julie, Howlett David R., Broadstock Martin, Hortobágyi Tibor, Ballard Clive, Thomas Alan J., O'Brien John T., Aarsland Dag, Attems Johannes, Francis Paul T., Whitfield David R.
Dátum:2017
ISSN:1387-2877
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Journal Of Alzheimers Disease 57 : 2 (2017), p. 373-386. -
További szerzők:Vallortigara, Julie Howlett, David R. Broadstock, Martin Hortobágyi Tibor (1965-) (patológus) Ballard, Clive G. Thomas, Alan O'Brien, John Aarsland, Dag Attems, Johannes Francis, Paul T. Whitfield, David
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2.

001-es BibID:BIBFORM082386
035-os BibID:(WoS)000528101100002 (Scopus)85084051209
Első szerző:Ashton, Nicholas J.
Cím:An update on blood-based biomarkers for non-Alzheimer neurodegenerative disorders / Nicholas J. Ashton, Abdul Hye, Anto P. Rajkumar, Antoine Leuzy, Stuart Snowden, Marc Suárez-Calvet, Thomas K. Karikari, Michael Schöll, Renaud La Joie, Gil D. Rabinovici, Kina Höglund, Clive Ballard1, Tibor Hortobágyi, Per Svenningsson, Kaj Blennow, Henrik Zetterberg, Dag Aarsland
Dátum:2020
ISSN:1471-003X 1471-0048
Megjegyzések:In recent years, there has been an increasing emphasis on the importance of blood-based biomarkers in the first-in-line evaluation of patients with suspected neurodegenerative disorders (NDD). While neuroimaging (structural and molecular) and cerebrospinal fluid (CSF) analyses identify the underlying pathophysiology at the earliest stage, a biologically relevant marker derived from blood would have greater utility in the primary care setting and in the early screening for eligibility for therapeutic trials. The rapid advancement of ultra-sensitive assays has enabled the investigation of pathological proteins to be measured in blood samples, but research has been predominately focused on Alzheimer's disease (AD) cohorts. Nonetheless, proteins that are currently under scrutiny as blood biomarker candidates for AD (amyloid-?, tau and neurofilament light chain) are likely to have importance for Lewy body dementia's (LBD), frontotemporal dementia's (FTD) and other NDDs in terms of shared pathologies, similar degenerative processes or in the differential diagnosis of clinical symptoms. This review gives an overview and update on the current state of blood-based biomarkers for non-AD NDD, focusing on how candidate AD and novel biomarkers perform in these populations. As background information, we also briefly outline the neuropathological, clinical, molecular imaging and CSF features of the most common NDDs outside of the AD continuum.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Nature Reviews Neuroscience. - 16 : 5 (2020), p. 265-284. -
További szerzők:Hye, Abdul Rajkumar, Anto P. Leuzy, Antoine Snowden, Stuart Suárez-Calvet, Marc Karikari, Thomas K. Schöll, Michael La Joie, Renaud Rabinovici, Gil D. Höglund, Kina Ballard, Clive G. Hortobágyi Tibor (1965-) (patológus) Svenningsson, Per Blennow, Kaj Zetterberg, Henrik Aarsland, Dag
Pályázati támogatás:(2017-1.2.1-NKP-2017-00002)
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Intézményi repozitóriumban (DEA) tárolt változat
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3.

001-es BibID:BIBFORM082378
035-os BibID:(cikkazonosító)5 (WoS)000455320300001 (Scopus)85059798236
Első szerző:Ashton, Nicholas J.
Cím:Increased plasma neurofilament light chain concentration correlates with severity of post-mortem neurofibrillary tangle pathology and neurodegeneration / Nicholas J. Ashton, Antoine Leuzy, Yau Mun Lim, Claire Troakes, Tibor Hortobágyi, Kina Höglund, Dag Aarsland, Simon Lovestone, Michael Schöll, Kaj Blennow, Henrik Zetterberg, Abdul Hye
Dátum:2019
ISSN:2051-5960
Megjegyzések:Alzheimer's disease (AD) is pathologically characterized by the accumulation of amyloid- (A) plaques, neurofibrillary tangles and widespread neuronal loss in the brain. In recent years, blood biomarkers have emerged as a realistic prospect to highlight accumulating pathology for secondary prevention trials. Neurofilament light chain (NfL), a marker of axonal degeneration, is robustly elevated in the blood of many neurological and neurodegenerative conditions, including AD. A strong relationship with cerebrospinal fluid (CSF) NfL suggests that these biomarker modalities reflect the same pathological process. Yet, the connection between blood NfL and brain tissue pathology has not been directly compared. In this study, longitudinal plasma NfL from cognitively healthy controls (n=12) and AD participants (n=57) were quantified by the Simoa platform. On reaching post-mortem, neuropathological assessment was performed on all participants, with additional frozen and paraffin-embedded tissue acquired from 26 participants for further biochemical (A(1-42), A(1-40), tau) and histological (NfL) evaluation. Plasma NfL concentrations were significantly increased in AD and correlated with cognitive decline, independent of age. Retrospective stratification based on Braak staging revealed that baseline plasma NfL concentrations were associated with higher neurofibrillary tangle pathology at post-mortem. Longitudinal increases in plasma NfL were observed in all Braak groupings; a significant negative association, however, was found between plasma NfL at time point 1 and both its rate of change and annual percentage increase. Immunohistochemical evaluation of NfL in the medial temporal gyrus (MTG) demonstrated an inverse relationship between Braak stages and NfL staining. Importantly, a significant negative correlation was found between the plasma NfL measurement closest to death and the level of NfL staining in the MTG at post-mortem. For the first time, we demonstrate that plasma NfL associates with the severity of neurofibrillary tangle pathology and neurodegeneration in the post-mortem brain.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Acta Neuropathologica Communications. - 7 : 1 (2019), p. 1-11. -
További szerzők:Leuzy, Antoine Lim, Yau Mun Troakes, Claire Hortobágyi Tibor (1965-) (patológus) Höglund, Kina Aarsland, Dag Lovestone, Simon Schöll, Michael Blennow, Kaj Zetterberg, Henrik Hye, Abdul
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4.

001-es BibID:BIBFORM029486
Első szerző:Auning, Eirik
Cím:Early and presenting symptoms of dementia with lewy bodies / Eirik Auning, Arvid Rongve, Tormod Fladby, Jan Booij, Tibor Hortobágyi, Francoise J. Siepel, Clive Ballard, Dag Aarsland
Dátum:2011
ISSN:1420-8008
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Dementia And Geriatric Cognitive Disorders. - 32 : 3 (2011), p. 202-208. -
További szerzők:Rongve, Arvid Fladby, Tormod Booij, Jan Hortobágyi Tibor (1965-) (patológus) Siepel, Francoise J. Ballard, Clive G. Aarsland, Dag
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5.

001-es BibID:BIBFORM063502
Első szerző:Baek, Jean-Ha
Cím:Unfolded protein response is activated in Lewy body dementias / J.-H. Baek, D. Whitfield, D. Howlett, P. Francis, E. Bereczki, C. Ballard, T. Hortobágyi, J. Attems, D. Aarsland
Dátum:2016
ISSN:0305-1846
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Neuropathology And Applied Neurobiology 42 : 4 (2016), p. 352-365. -
További szerzők:Whitfield, David Howlett, David R. Francis, Paul T. Bereczki Erika Ballard, Clive G. Hortobágyi Tibor (1965-) (patológus) Attems, Johannes Aarsland, Dag
Internet cím:DOI
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6.

001-es BibID:BIBFORM083679
Első szerző:Bencze János (orvos)
Cím:Dementia with Lewy bodies - a clinicopathological update / János Bencze, Woosung Seo, Abdul Hye, Dag Aarsland, Tibor Hortobágyi
Dátum:2020
Megjegyzések:Dementia is one of the major burdens of our aging society. According to certain predictions, the number of patients will double every 20 years. Although Alzheimer's disease (AD), as the most frequent neurodegenera-tive dementia, has been extensively analysed, less is known about dementia with Lewy bodies (DLB). Neuropa-thological hallmarks of DLB are the deposition of intracellular Lewy bodies (LB) and Lewy neurites (LN). DLB belongs to the ?-synucleinopathies, as the major component of these inclusions is pathologically aggregated ?-synuclein. Depending on the localizationof LBs and LNs in the central nervous system cognitive and motor symptoms can occur. In our work, we will systematically review the possible etiology and epidemiology, patho-logical (both macroscopic and microscopic) features, structural and functional imaging findings, with a special emphasis on the clinico-pathological correlations. Finally, we summarize the latest clinical symptoms-based diagnostic criteria and the novel therapeutic approaches. Since DLB is frequently accompanied with AD pathol-ogy, highlighting possible differential diagnostic approaches is an integral part of our paper. Although our pre-sent knowledge is insufficient, the rapid development of diagnostic and research methodsprovide hope for better diagnosis and more efficient treatment, contributing to a better quality of life.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Free Neuropathology. - 1 (2020), p. 1-12. -
További szerzők:Seo, Woosung Hye, Abdul Aarsland, Dag Hortobágyi Tibor (1965-) (patológus)
Pályázati támogatás:EFOP-3.6.3-VEKOP-16-2017-00009
EFOP
GINOP-2.3.2-15-2016-00043
GINOP
NAP (2017-1.2.1-NKP-2017-00002)
Egyéb
ÚNKP-19-3
Egyéb
NKFIH SNN 132999
Egyéb
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7.

001-es BibID:BIBFORM083135
035-os BibID:(cikkazonosító)68 (scopus)85078993240 (wos)000519243400011
Első szerző:Bencze János (orvos)
Cím:Lemur tyrosine kinase 2 (LMTK2) level inversely correlates with phospho-tau in neuropathological stages of Alzheimer's disease / János Bencze, Máté Szarka, Viktor Bencs, Renáta Nóra Szabó, László V. Módis, Dag Aarsland, Tibor Hortobágyi
Dátum:2020
Megjegyzések:Alzheimer's disease (AD) is the most common neurodegenerative dementia. Mapping the pathomechanism and providing novel therapeutic options have paramount significance. Recent studies have proposed the role of LMTK2 in AD. However, its expression pattern and association with the pathognomonic neurofibrillary tangles (NFTs) in different brain regions and neuropathological stages of AD is not clear. We performed chromogenic (CHR) LMTK2 and fluorescent phospho-tau/LMTK2 double-labelling (FDL) immunohistochemistry (IHC) on 10-10 post-mortem middle frontal gyrus (MFG) and anterior hippocampus (aHPC) samples with early and late neuropathological Braak tau stages of AD. MFG in early stage was our ♭endogenous control' region as it is not affected by NFTs. Semi-quantitative CHR-IHC intensity scoring revealed significantly higher (p<0.001) LMTK2 values in this group compared to NFT-affected regions. FDL-IHC demonstrated LMTK2 predominance in the endogenous control region, while phospho-tau overburden and decreased LMTK2 immunolabelling were detected in NFT-affected groups (aHPC in early and both regions in late stage). Spearman's correlation coefficient showed strong negative correlation between phospho-tau/LMTK2 signals within each group. According to our results LMTK2 expression is inversely proportionate to the extent of NFT pathology, as well as decreased LMTK2 level is not a general feature in AD brain, rather it is characteristic to the NFT-affected regions.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Alzheimer's disease
LMTK2
neurodegeneration
tau
digital image analysis
Megjelenés:Brain Sciences. - 10 : 2 (2020), p. 1-14. -
További szerzők:Szarka Máté (1990-) Bencs Viktor (1995-) (orvos) Szabó Renáta Nóra Módis László V. (neurológus) Aarsland, Dag Hortobágyi Tibor (1965-) (patológus)
Pályázati támogatás:EFOP-3.6.3-VEKOP-16-2017-00009
EFOP
ÚNKP-19-3
Egyéb
NAP (2017-1.2.1-NKP-2017-00002)
Egyéb
GINOP-2.3.2-15-2016-00043
GINOP
ÚNKP-19-2
Egyéb
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8.

001-es BibID:BIBFORM081788
035-os BibID:(cikkazonosító)17222 (WOS)000497712500018 (Scopus)85075476757
Első szerző:Bencze János (orvos)
Cím:Neuropathological characterization of Lemur tyrosine kinase 2 (LMTK2) in Alzheimer's disease and neocortical Lewy body disease / János Bencze, Máté Szarka, Viktor Bencs, Renáta Nóra Szabó, Máté Smajda, Dag Aarsland, Tibor Hortobágyi
Dátum:2019
ISSN:2045-2322
Megjegyzések:Alzheimer's disease (AD) and neocortical Lewy body disease (LBD) are the most common neurodegenerative dementias, with no available curative treatment. Elucidating pathomechanism and identifying novel therapeutic targets is of paramount importance. Lemur tyrosine kinase 2 (LMTK2) is involved in several physiological and pathological cellular processes. Herewith a neuropathological characterization is presented in AD and neocortical LBD samples using chromogenic and fluorescent LMTK2 immunohistochemistry on post-mortem brain tissues and compared them to age-matched controls (CNTs). LMTK2 immunopositivity was limited to the neuronal cytoplasm. Neurons, including tau-positive tangle-bearing ones, showed decreased chromogenic and immunofluorescent labelling in AD in every cortical layer compared to CNT and neocortical LBD. Digital image analysis was performed to measure the average immunopositivity of groups. Mean grey values were calculated for each group after measuring the grey scale LMTK2 signal intensity of each individual neuron. There was significant difference between the mean grey values of CNT vs. AD and neocortical LBD vs. AD. The moderate decrease in neocortical LBD suggests the effect of coexisting AD pathology. We provide neuropathological evidence on decreased neuronal LMTK2 immunolabeling in AD, with implications for pathogenesis.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Scientific Reports. - 9 : 1 (2019), p. 1-9. -
További szerzők:Szarka Máté (1990-) Bencs Viktor (1995-) (orvos) Szabó Renáta Nóra Smajda Máté Aarsland, Dag Hortobágyi Tibor (1965-) (patológus)
Pályázati támogatás:EFOP-3.6.3-VEKOP-16-2017-00009
EFOP
GINOP-2.3.2-15-2016-00043
GINOP
ÚNKP-19-3
Egyéb
ÚNKP-18-3
Egyéb
ÚNKP-19-2
Egyéb
2017-1.2.1-NKP-2017-00002
MTA
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9.

001-es BibID:BIBFORM071437
Első szerző:Bereczki Erika
Cím:Synaptic markers of cognitive decline in neurodegenerative diseases : a proteomic approach / Erika Bereczki, Rui M. Branca, Paul T. Francis, Joana B. Pereira, Jean-Ha Baek, Tibor Hortobágyi, Bengt Winblad, Clive Ballard, Janne Lehtiö, Dag Aarsland
Dátum:2017
ISSN:0006-8950
Megjegyzések:See Attems and Jellinger (doi:10.1093/brain/awx360) for a scientific commentary on this article.Cognitive changes occurring throughout the pathogenesis of neurodegenerative diseases are directly linked to synaptic loss. We used in-depth proteomics to compare 32 post-mortem human brains in the prefrontal cortex of prospectively followed patients with Alzheimer's disease, Parkinson's disease with dementia, dementia with Lewy bodies and older adults without dementia. In total, we identified 10 325 proteins, 851 of which were synaptic proteins. Levels of 25 synaptic proteins were significantly altered in the various dementia groups. Significant loss of SNAP47, GAP43, SYBU (syntabulin), LRFN2, SV2C, SYT2 (synaptotagmin 2), GRIA3 and GRIA4 were further validated on a larger cohort comprised of 92 brain samples using ELISA or western blot. Cognitive impairment before death and rate of cognitive decline significantly correlated with loss of SNAP47, SYBU, LRFN2, SV2C and GRIA3 proteins. Besides differentiating Parkinson's disease dementia, dementia with Lewy bodies, and Alzheimer's disease from controls with high sensitivity and specificity, synaptic proteins also reliably discriminated Parkinson's disease dementia from Alzheimer's disease patients. Our results suggest that these particular synaptic proteins have an important predictive and discriminative molecular fingerprint in neurodegenerative diseases and could be a potential target for early disease intervention.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Brain 141 : 2 (2018), p. 582-595. -
További szerzők:Branca, Rui M. Francis, Paul T. Pereira, Joana B. Baek, Jean-Ha Hortobágyi Tibor (1965-) (patológus) Winblad, Bengt Ballard, Clive G. Lehtiö, Janne Aarsland, Dag
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10.

001-es BibID:BIBFORM063546
Első szerző:Bereczki Erika
Cím:Synaptic proteins predict cognitive decline in Alzheimer's disease and Lewy body dementia / Erika Bereczki, Paul T. Francis, David Howlett, Joana B. Pereira, Kina Höglund, Anna Bogstedt, Angel Cedazo-Minguez, Jean-Ha Baek, Tibor Hortobágyi, Johannes Attems, Clive Ballard, Dag Aarsland
Dátum:2016
ISSN:0893-0341
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Alzheimers & Dementia 12 : 11 (2016), p. 1149-1158. -
További szerzők:Francis, Paul T. Howlett, David R. Pereira, Joana B. Höglund, Kina Bogstedt, Anna Cedazo-Minguez, Angel Baek, Jean-Ha Hortobágyi Tibor (1965-) (patológus) Attems, Johannes Ballard, Clive G. Aarsland, Dag
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11.

001-es BibID:BIBFORM022141
Első szerző:Fritze, Friederike
Cím:Depressive symptoms in Alzheimer's disease and Lewy body dementia : a one-year follow-up study / Friederike Fritze, Uwe Ehrt, Tibor Hortobagyi, Clive Ballard, Dag Aarsland
Dátum:2011
ISSN:1420-8008
Megjegyzések:Objective: To explore the course of depression in people with mild dementia and identify predictors for depression at 1-year follow-up. Methods: Patients with mild dementia (n = 199) were assessed using Montgomery and Åsberg Depression Rating Scale (MADRS) and the depression item from Neuropsychiatric Inventory (NPI) at baseline and after 1 year. A score above 6 on MADRS indicates at least mild depression. Linear and logistic regression analyses were performed to identify predictors of change in depression scores. Results: Among subjects with depression at baseline, 68.1% remained depressed at follow-up, whereas 31.9% had remitted, based on MADRS. Among patients without depression at baseline, 77.1% remained non-depressed at follow-up, whereas 22.9% had incident depression. The proportion with persistent depression was higher in the combined dementia with Lewy bodies (DLB)/Parkinson's disease with dementia (PDD) group (45.5%) compared to AD (28%) (p < 0.05). Greater decline on the Mini Mental State Examination (p < 0.001) and higher baseline MADRS score (p < 0.001) were significant predictors of increased MADRS score. Conclusion: Two thirds of patients with depression at baseline were still depressed at follow-up, more so in DLB with PDD compared to AD. Cognitive decline was associated with worsening of depressive symptoms.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Dementia and Geriatric Cognitive Disorders. - 32 : 2 (2011), p. 143-149. -
További szerzők:Ehrt, Uwe Hortobágyi Tibor (1965-) (patológus) Ballard, Clive G. Aarsland, Dag
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12.

001-es BibID:BIBFORM020291
Első szerző:Fritze, Friederike
Cím:Depression in mild dementia : associations with diagnosis, APOE genotype and clinical features / Friederike Fritze, Uwe Ehrt, Hogne Sønnesyn, Martin Kurz, Tibor Hortobágyi, Sabine Piepenstock Nore, Clive Ballard, Dag Aarsland
Dátum:2011
ISSN:0885-6230
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:International Journal of Geriatric Psychiatry. - 26 : 10 (2011), p. 1054-1061. -
További szerzők:Ehrt, Uwe Sønnesyn, Hogne Kurz, Martin Hortobágyi Tibor (1965-) (patológus) Nore, Sabine Piepenstock Ballard, Clive G. Aarsland, Dag
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