| 1. |
- Abdelnour, C., et al.
(författare)
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Alzheimer's disease cerebrospinal fluid biomarkers predict cognitive decline in lewy body dementia
- 2016
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 31:8, s. 1203-1208
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionAlzheimer's disease pathologies are common in dementia with Lewy bodies, but their clinical relevance is not clear. CSF biomarkers amyloid beta 1-42, total tau, and tau phosphorylated at threonine 181 reflect Alzheimer's disease neuropathology antemortem. In PD, low CSF amyloid beta 1-42 predict long-term cognitive decline, but little is known about these biomarkers as predictors for cognitive decline in Lewy body dementia. The aim of this study was to assess whether Alzheimer's disease CSF biomarkers predict cognitive decline in Lewy body dementia. MethodsFrom a large European dementia with Lewy bodies multicenter study, we analyzed baseline Alzheimer's disease CSF biomarkers and serial MMSE (baseline and 1- and 2-year follow-up) in 100 patients with Lewy body dementia. Linear mixed-effects analyses, adjusted for sex, age, baseline MMSE, and education, were performed to model the association between CSF biomarkers and rate of cognitive decline measured with MMSE. An Alzheimer's disease CSF profile was defined as pathological amyloid beta 1-42 plus pathological total tau or phosphorylated tau. ResultsThe Alzheimer's disease CSF profile, and pathological levels of amyloid beta 1-42, were associated with a more rapid decline in MMSE (2.2 [P < 0.05] and 2.9 points difference [P < 0.01], respectively). Higher total tau values showed a trend toward association without statistical significance (2.0 points difference; P = 0.064), whereas phosphorylated tau was not associated with decline. ConclusionsReduced levels of CSF amyloid beta 1-42 were associated with more rapid cognitive decline in Lewy body dementia patients. Future prospective studies should include larger samples, centralized CSF analyses, longer follow-up, and biomarker-pathology correlation. (c) 2016 International Parkinson and Movement Disorder Society
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| 2. |
- Ayton, Scott, et al.
(författare)
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The Neuroinflammatory Acute Phase Response in Parkinsonian-Related Disorders
- 2022
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 37:5, s. 993-1003
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neuroinflammation is implicated in the pathophysiology of Parkinson's disease (PD) and related conditions, yet prior clinical biomarker data report mixed findings. Objectives: The aim was to measure a panel of neuroinflammatory acute phase response (APR) proteins in the cerebrospinal fluid (CSF) of participants with PD and related disorders. Methods: Eleven APR proteins were measured in the CSF of 867 participants from the BioFINDER cohort who were healthy (612) or had a diagnosis of PD (155), multiple system atrophy (MSA) (26), progressive supranuclear palsy (PSP) (22), dementia with Lewy bodies (DLB) (23), or Parkinson’s disease with dementia (PDD) (29). Results: CSF APR proteins were mostly unchanged in PD, with only haptoglobin and α1-antitrypsin significantly elevated compared to controls. These proteins were variably increased in the other disorders. Certain protein components yielded unique signatures according to diagnosis: ferritin and transthyretin were selectively elevated in MSA and discriminated these patients from all others. Haptoglobin was selectively increased in PSP, discriminating this disease from MSA when used in combination with ferritin and transthyretin. This panel of proteins did not correlate well with severity of motor impairment in any disease category, but several (particularly ceruloplasmin and ferritin) were associated with memory performance (Mini-Mental State Examination) in patients with DLB and PDD. Conclusions: These findings provide new insights into inflammatory changes in PD and related disorders while also introducing biomarkers of potential clinical diagnostic utility.
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| 3. |
- Barbu, Andrea R, et al.
(författare)
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Gene Therapy
- 2010. - 4th edition
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Ingår i: Textbook of Diabetes. - Thousand Oaks, CA : Wiley-Blackwell. - 9781405191814 ; 25, s. 604-604
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Bezard, Erwan, et al.
(författare)
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Animal Models of Parkinson's Disease: Limits and Relevance to Neuroprotection Studies
- 2013
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 28:1, s. 61-70
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Forskningsöversikt (refereegranskat)abstract
- Over the last two decades, significant strides has been made toward acquiring a better knowledge of both the etiology and pathogenesis of Parkinson's disease (PD). Experimental models are of paramount importance to obtain greater insights into the pathogenesis of the disease. Thus far, neurotoxin-based animal models have been the most popular tools employed to produce selective neuronal death in both in vitro and in vivo systems. These models have been commonly referred to as the pathogenic models. The current trend in modeling PD revolves around what can be called the disease gene-based models or etiologic models. The value of utilizing multiple models with a different mechanism of insult rests on the premise that dopamine-producing neurons die by stereotyped cascades that can be activated by a range of insults, from neurotoxins to downregulation and overexpression of disease-related genes. In this position article, we present the relevance of both pathogenic and etiologic models as well as the concept of clinically relevant designs that, we argue, should be utilized in the preclinical development phase of new neuroprotective therapies before embarking into clinical trials. (C) 2012 Movement Disorder Society
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| 5. |
- Bezard, Erwan, et al.
(författare)
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Study of the antidyskinetic effect of eltoprazine in animal models of levodopa-induced dyskinesia
- 2013
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 28:8, s. 1088-1096
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Tidskriftsartikel (refereegranskat)abstract
- The serotonin (5-hydroxytryptamine [5HT]) system has recently emerged as an important player in the appearance of l-3,4-dihydroxyphenylalanine (levodopa [l-dopa])-induced dyskinesia in animal models of Parkinson's disease. In fact, dopamine released as a false transmitter from serotonin neurons appears to contribute to the pulsatile stimulation of dopamine receptors, leading to the appearance of the abnormal involuntary movements. Thus, drugs able to dampen the activity of serotonin neurons hold promise for the treatment of dyskinesia. The authors investigated the ability of the mixed 5-HT 1A/1B receptor agonist eltoprazine to counteract l-dopa-induced dyskinesia in 6-hydroxydopamine-lesioned rats and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaques. The data demonstrated that eltoprazine is extremely effective in suppressing dyskinesia in experimental models, although this effect was accompanied by a partial worsening of the therapeutic effect of l-dopa. Interestingly, eltoprazine was found to (synergistically) potentiate the antidyskinetic effect of amantadine. The current data indicated that eltoprazine is highly effective in counteracting dyskinesia in preclinical models. However, the partial worsening of the l-dopa effect observed after eltoprazine administration represents a concern; whether this side effect is due to a limitation of the animal models or to an intrinsic property of eltoprazine needs to be addressed in ongoing clinical trials. The data also suggest that the combination of low doses of eltoprazine with amantadine may represent a valid strategy to increase the antidyskinetic effect and reduce the eltoprazine-induced worsening of l-dopa therapeutic effects. (c) 2013 Movement Disorder Society
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| 6. |
- Björklund, Anders, et al.
(författare)
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Cell therapy for Parkinson's disease: what next?
- 2013
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 28:1, s. 110-115
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Tidskriftsartikel (refereegranskat)abstract
- The idea to use transplants of dopamine-producing cells to substitute for the lost midbrain dopamine neurons in Parkinson's disease (PD) goes back to the 1970s. In this review we give an overview of the history of cell transplantation in animal models of PD, and summarize the experience gained from the open-label and placebo-controlled clinical trials performed so far using intrastriatal transplants of human fetal dopamine neuroblasts. Further development of this therapeutic approach face numerous challenges, for example in the development of protocols that allow generation of fully functional and safe midbrain dopamine neurons from stem cells. Based on recent promising advancements, efforts are now being made to develop standardized and efficient protocols, and adapt these protocols to good laboratory practice (GLP)/good manufacturing practice (GMP) conditions, to move this technology closer to clinical translation. © 2013 Movement Disorder Society.
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| 7. |
- Björklund, Tomas, et al.
(författare)
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Gene therapy for Parkinson's disease.
- 2010
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 25 Suppl 1, s. 161-173
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Tidskriftsartikel (refereegranskat)abstract
- The once fantastic theoretical concept that patients with Parkinson's disease (PD) would receive gene therapy in an attempt to alleviate their symptoms and potentially modify the course of their disease has become a reality. On the basis of positive preclinical data, four different gene therapy approaches are currently in Phase I or Phase II clinical trials. Some approaches are intended to increase levels of endogenous dopamine or enhance the function of the prodrug levodopa. Others are intended to normalize basal ganglia circuitry by reducing the PD-related overactivity of specific brain structures such as the subthalamic nucleus. Each is intended for symptomatic benefit. Finally, gene delivery of trophic factors that not only augment dopaminergic function but are potentially disease modifying has a strong preclinical database and are also in clinical trials. Each of these approaches is discussed in the present review.
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