| 11. |
- Javanshiri, Keivan, et al.
(författare)
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Cardiac Alpha-Synuclein Is Present in Alpha-Synucleinopathies
- 2022
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Ingår i: Journal of Parkinson's Disease. - 1877-718X. ; 12:4, s. 1125-1131
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alpha-synucleinopathies (AS) are characterized by pathologic aggregations of alpha-synuclein (α-syn) in the central nervous system, and comprise dementia with Lewy bodies, Parkinson's disease, and multiple system atrophy. Previous studies on AS have reported findings of α-syn pathology in the peripheral nervous system of multiple organs, including the heart.Objective: The aim of this study was to further investigate and confirm the presence of cardiac α-syn in AS compared to other major neurocognitive disorders in a neuropathologically confirmed cohort.Methods: All deceased patients with performed autopsy and with neuropathologically confirmed AS at the Clinical Department of Pathology in Lund 2010-May 2021 were evaluated for inclusion. Cases with insufficiently sampled cardiac tissue or only limited neuropathological investigation were excluded. An age-matched group of individuals with other neurodegenerative diseases, having no α-syn in the CNS, served as controls. In total, 68 AS and 32 control cases were included in the study. Immunohistochemistry for detection of cardiac α-syn aggregates was performed.Results: The AS group had a significantly higher prevalence of cardiac α-syn pathology (p≤0.001) than the control group, 82% and 0%, respectively.Conclusion: This study confirms the association between AS and the presence of cardiac α-syn in a neuropathologically confirmed cohort. This motivates further research on potential pathophysiological effects on cardiac function in AS patients.
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| 12. |
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| 13. |
- Kumar, Abhishek, et al.
(författare)
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Chewing and its influence on swallowing, gastrointestinal and nutrition-related factors : a systematic review
- 2022
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Ingår i: Critical Reviews in Food Science and Nutrition. - : Taylor and Francis Ltd.. - 1040-8398 .- 1549-7852. ; , s. 1-31
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Forskningsöversikt (refereegranskat)abstract
- The study aimed to evaluate the hypothesis that chewing is a mechanical and physiological contributor to swallowing, physiologic/pathologic processes of the gastrointestinal tract (GIT), and nutrition-related factors. A search strategy was applied to three different databases to investigate if chewing function in adults affects the swallowing, physiologic/pathologic processes of the GIT, and nutrition-related factors compared to controls with no exposure. The included studies were evaluated for methodological quality and risk of bias and certainty of evidence. The results showed 71 eligible studies. Overall, the results showed that 46 studies supported the hypothesis while 25 refuted it. However, the GRADE analysis showed low to very low certainty of the evidence to support the hypothesis that chewing is an important contributor in the swallowing process, and physiologic/pathologic processes in the GIT. The GRADE analysis also showed a moderate to very low certainty of the evidence to suggest that chewing function contributes to nutrition-related parameters. The overall results of the current study showed that a majority (64.7%) of the studies (46 out of 71) supported the hypothesis. However, robust studies with proper design, adequate sample size, and well-defined outcome parameters are needed to establish conclusive evidence.
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| 14. |
- Lindblom, Rickard, 1981-, et al.
(författare)
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Mechanical Reperfusion Following Prolonged Global Cerebral Ischemia Attenuates Brain Injury
- 2021
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Ingår i: Journal of Cardiovascular Translational Research. - : Springer Science and Business Media LLC. - 1937-5387 .- 1937-5395. ; 14:2, s. 338-347
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Tidskriftsartikel (refereegranskat)abstract
- Previous experiments demonstrated improved outcome following prolonged cerebral ischemia given controlled brain reperfusion using extracorporeal circulation. The current study further investigates this. Young adult pigs were exposed to 30 min of global normothermic cerebral ischemia, achieved through intrathoracic clamping of cerebral arteries, followed by 20 min of isolated mechanical brain reperfusion. Leukocyte-filtered blood was delivered by a roller-pump at fixed pressure and flow. One experimental group additionally had a custom-made buffer solution delivered at 1:8 ratio with the blood. Hemodynamics including intracranial pressure were monitored. Blood gases were from peripheral arteries and the sagittal sinus, and intraparenchymal brain microdialysis was performed. The brains were examined by a neuropathologist. The group with the added buffer showed lower intracranial pressure as well as decreased intraparenchymal glycerol and less signs of excitotoxicity and ischemia, although histology revealed similar degrees of injury. A customized mechanical reperfusion improves multiple parameters after prolonged normothermic global cerebral ischemia. [Figure not available: see fulltext.]
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| 15. |
- Matti, Nathalie, et al.
(författare)
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Locus Coeruleus Degeneration Differs Between Frontotemporal Lobar Degeneration Subtypes
- 2022
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877. ; 89:2, s. 463-471
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are few studies on the locus coeruleus (LC) in frontotemporal lobar degeneration (FTLD) and the potential differences in the LC related to the underlying proteinopathy. Objective: The aim of this study was to investigate the LC in FTLD subgroups. Methods: Neuropathological cases diagnosed with FTLD were included. The subgroups consisted of FTLD with tau, transactive response DNA-binding protein 43 (TDP) and fused in sarcoma (FUS). Micro-and macroscopical degeneration of the LC were assessed with respect to the number of neurons and the degree of depigmentation. A group of cognitively healthy subjects and a group with vascular cognitive impairment (VCI) served as comparison groups. Results: A total of 85 FTLD cases were included, of which 44 had FTLD-TDP, 38 had FTLD-tau, and three had FTLD-FUS. The groups were compared with 25 VCI cases and 41 cognitively healthy control cases (N = 151 for the entire study). All FTLD groups had a statistically higher microscopical degeneration of the LC compared to the controls, but the FTLD-tau group had greater micro-and macroscopical degeneration than the FTLD-TDP group. Age correlated positively with the LC score in the FTLD-tau group, but not in the FTLD-TDP group. Conclusion: A greater microscopical degeneration of the LC was observed in all FTLD cases compared to healthy controls and those with VCI. The LC degeneration was more severe in FTLD-tau than in FTLD-TDP. The macroscopically differential degeneration of the LC in FTLD subgroups may facilitate differential diagnostics, potentially with imaging.
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| 16. |
- Niklasson, Bo, et al.
(författare)
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Picornavirus May Be Linked to Parkinson’s Disease through Viral Antigen in Dopamine-Containing Neurons of Substantia Nigra
- 2022
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Ingår i: Microorganisms. - : MDPI AG. - 2076-2607. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson’s disease (PD) is a neurodegenerative disease linked with the loss of dopaminer-gic neurons in the brain region called substantia nigra and caused by unknown pathogenic mecha-nisms. Two currently recognized prominent features of PD are an inflammatory response manifested by glial reaction and T-cell infiltration, as well as the presence of various toxic mediators derived from activated glial cells. PD or parkinsonism has been described after infection with several different viruses and it has therefore been hypothesized that a viral infection might play a role in the pathogen-esis of the disease. We investigated formalin-fixed post-mortem brain tissue from 9 patients with Parkinson’s disease and 11 controls for the presence of Ljungan virus (LV) antigen using a polyclonal antibody against the capsid protein of this recently identified picornavirus with neurotropic proper-ties, suspected of being both a human and an animal pathogen. Evidence of viral antigen was found in 7 out of 9 Parkinson’s disease cases and in only 1 out of 11 controls (p = 0.005). The picornavirus antigen was present in dopamine-containing neurons of the substantia nigra. We propose that LV or an LV-related virus initiates the pathological process underlying sporadic PD. LV-related picornavirus antigen has also been reported in patients with Alzheimer’s disease. Potentially successful antiviral treatment in Alzheimer’s disease suggests a similar treatment for Parkinson's disease. Amanta-dine, originally developed as an antiviral drug against influenza infection, has also been used for symptomatic treatment of patients with PD for more than 50 years and is still commonly used by neurologists today. The fact that amantadine also has an antiviral effect on picornaviruses opens the question of this drug being re-evaluated as potential PD therapy in combination with other antiviral compounds directed against picornaviruses.
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| 17. |
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| 18. |
- Respondek, Gesine, et al.
(författare)
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Validation of the movement disorder society criteria for the diagnosis of 4-repeat tauopathies
- 2020
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 35:1, s. 171-176
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Movement Disorder Society criteria for progressive supranuclear palsy introduced the category “probable 4-repeat (4R)-tauopathy” for joint clinical diagnosis of progressive supranuclear palsy and corticobasal degeneration. Objectives: To validate the accuracy of these clinical criteria for “probable 4R-tauopathy” to predict underlying 4R-tauopathy pathology. Methods: Diagnostic accuracy for 4R-tauopathies according to the established criteria was estimated retrospectively in autopsy-confirmed patients with progressive supranuclear palsy and corticobasal degeneration (grouped as 4R-tauopathies), and Parkinson's disease, multiple system atrophy, and frontotemporal lobar degeneration (grouped as non-4R-tauopathies). Results: We identified 250 cases with progressive supranuclear palsy (N = 195) and corticobasal degeneration (N = 55) and with and non-4R-tauopathies (N = 161). Sensitivity and specificity of “probable 4R-tauopathy” was 10% and 99% in the first year and 59% and 88% at final record. Conclusions: The new diagnostic category “probable 4R-tauopathy” showed high specificity and may be suitable for the recruitment of patients with progressive supranuclear palsy and corticobasal degeneration into therapeutic trials targeting 4R-tauopathy. The low sensitivity underpins the need for diagnostic biomarkers.
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| 19. |
- Roeder, SS, et al.
(författare)
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Evidence for postnatal neurogenesis in the human amygdala
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 366-
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Tidskriftsartikel (refereegranskat)abstract
- The human amygdala is involved in processing of memory, decision-making, and emotional responses. Previous studies suggested that the amygdala may represent a neurogenic niche in mammals. By combining two distinct methodological approaches, lipofuscin quantification and 14C-based retrospective birth dating of neurons, along with mathematical modelling, we here explored whether postnatal neurogenesis exists in the human amygdala. We investigated post-mortem samples of twelve neurologically healthy subjects. The average rate of lipofuscin-negative neurons was 3.4%, representing a substantial proportion of cells substantially younger than the individual. Mass spectrometry analysis of genomic 14C-concentrations in amygdala neurons compared with atmospheric 14C-levels provided evidence for postnatal neuronal exchange. Mathematical modelling identified a best-fitting scenario comprising of a quiescent and a renewing neuronal population with an overall renewal rate of >2.7% per year. In conclusion, we provide evidence for postnatal neurogenesis in the human amygdala with cell turnover rates comparable to the hippocampus.
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| 20. |
- Rosenstein, Igal, 1984, et al.
(författare)
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Four Swedish cases of CSF1R-related leukoencephalopathy: Visualization of clinical phenotypes
- 2022
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 145:5, s. 599-609
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Tidskriftsartikel (refereegranskat)abstract
- Colony stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is a rare, genetic disease caused by heterozygous mutations in the CSF1R gene with rapidly progressive neurodegeneration, behavioral, cognitive, motor disturbances. Objective: To describe four cases of CSF1R-related leukoencephalopathy from three families with two different pathogenic mutations in the tyrosine kinase domain of CSF1R and to develop an integrated presentation of inter-individual diversity of clinical presentations. Methods: This is an observational study of a case series. Patients diagnosed with CSF1R encephalopathy were evaluated with standardized functional estimation scores and subject to analysis of cerebrospinal fluid biomarkers. Brain computed tomography (CT) and magnetic resonance imaging (MRI) were evaluated. We performed a functional phosphorylation assay to confirm the dysfunction of mutated CSF1R protein. Results: Two heterozygous missense mutations in the CSF1R gene were identified, c.2344C>T; p.Arg777Trp and c.2329C>T; p.Arg782Cys. A phosphorylation assay in vitro showed markedly reduced autophosphorylation in cells expressing mutations. According to ACMG criteria, both mutations were pathogenic. A radiological investigation revealed typical white matter lesions in all cases. There was inter-individual diversity in the loss of cognitive, motor-neuronal, and extrapyramidal functions. Conclusions: Including the present cases, currently three CSF1R mutations are known in Sweden. We present a visualization tool to describe the clinical diversity, with potential use for longitudinal follow-up for this and other leukoencephalopathies.
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