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Sökning: LAR1:gu > Forskningsöversikt > Mattsson Niklas 1979

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2.
  • Mattsson, Niklas, 1979 (författare)
  • CSF biomarkers in neurodegenerative diseases.
  • 2011
  • Ingår i: Clinical chemistry and laboratory medicine : CCLM / FESCC. - 1434-6621. ; 49:3, s. 345-52
  • Forskningsöversikt (refereegranskat)abstract
    • Neurodegenerative diseases are major world wide causes of morbidity and mortality. They form a heterogeneous group of diseases, ranging from rare monogenic inherited errors of metabolism to common multi-factorial dementias. Major research efforts focus on the development of disease modifying drugs for neurodegenerative diseases. As a result, there follows a need for reliable tools for diagnosis, prognosis and monitoring of therapy. Processes in the brain can be monitored by analysis of cerebrospinal fluid (CSF). Several CSF biomarkers of pathological processes in the brain are now available. Such biomarkers may be used for both research and in the clinical setting. However, several difficult problems remain to be solved. More intensive collaboration between academia, industry and government is likely needed to develop treatments and biomarkers for neurodegenerative diseases. This article reviews the definitions, usage and current limitations of CSF biomarkers in this field.
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3.
  • Mattsson, Niklas, 1979, et al. (författare)
  • CSF biomarkers: pinpointing Alzheimer pathogenesis.
  • 2009
  • Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 1749-6632 .- 0077-8923. ; 1180, s. 28-35
  • Forskningsöversikt (refereegranskat)abstract
    • Intense research during the last decades has resulted in an unprecedented accumulation of knowledge regarding the pathogenesis of Alzheimer's disease. Primarily, the focus has been directed toward amyloid and tau pathology and their relations to synaptic and neuronal loss. However, as the complexity of the disease becomes increasingly evident, the importance of other factors, such as inflammation, oxidative stress, and mitochondrial dysfunction, grow apparent. Here, we review available CSF biomarkers for these pathological processes. We also consider their usability in clinical practice and in clinical trials.
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4.
  • Mattsson, Niklas, 1979, et al. (författare)
  • Future screening for incipient Alzheimer's disease--the influence of prevalence on test performance.
  • 2009
  • Ingår i: European neurology. - : S. Karger AG. - 1421-9913 .- 0014-3022. ; 62:4, s. 200-3
  • Forskningsöversikt (refereegranskat)abstract
    • Much effort has been made to identify and verify diagnostic biomarkers for early stage Alzheimer's disease (AD). The need for this is often advocated by possible future disease-modifying treatments, likely to be most effective if initiated early in the disease process. Since the neurodegenerative process probably starts many years before the first onset of symptoms, such future drugs are likely to invoke a need for screening presymptomatic individuals. Here, we speculate on the performance of currently available AD biomarkers in hypothetical screening programs of different designs. We note that many diagnostic tests will have an excellent ability to exclude upcoming AD. However, even the best tests will suffer from poor positive predictive values given the relatively low disease prevalence in populations with no or very few symptomatic individuals, also when taking future converters to AD into account. The magnitude of this problem, which is common among most screening programs, will depend on the efficacy, safety and cost of the future anti-AD drugs. A number of tentative solutions to the problem, apart from better tests, are discussed.
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5.
  • Mattsson, Niklas, 1979, et al. (författare)
  • Inter-laboratory variation in cerebrospinal fluid biomarkers for Alzheimer's disease: united we stand, divided we fall.
  • 2010
  • Ingår i: Clinical chemistry and laboratory medicine : CCLM / FESCC. - 1434-6621. ; 48:5, s. 603-7
  • Forskningsöversikt (refereegranskat)abstract
    • Abstract Several drug candidates for Alzheimer's disease are being evaluated in clinical trials, with the goal of finding a drug with disease-modifying effects. When such a drug finally reaches the market, there will be a demand for accurate diagnostic tools useful for early detection of disease and for monitoring biochemical effects. The core cerebrospinal fluid (CSF) biomarkers amyloid peptides (Abeta42), total-tau and phospo-tau are promising in this respect. However, inter-center variation (caused by pre-analytical, analytical and post-analytical factors), and inter-laboratory variation (caused by analytical factors), particularly for CSF Abeta42, lowers their utility in multicenter studies. Here, we discuss the causes of these variations, and present a global quality control program to overcome them.
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6.
  • Mattsson, Niklas, 1979, et al. (författare)
  • Lessons from Multicenter Studies on CSF Biomarkers for Alzheimer's Disease.
  • 2010
  • Ingår i: International journal of Alzheimer's disease. - : Hindawi Limited. - 2090-0252. ; 2010
  • Forskningsöversikt (refereegranskat)abstract
    • Several single-center studies have confirmed the usability of cerebrospinal fluid (CSF) biomarkers for the diagnosis of Alzheimer's disease (AD), even in early disease stages. Large scale multicenter studies have principally confirmed this, although such studies have also indicated the presence of significant intercenter and interlaboratory variations in biomarker measurements. Such variations may hamper the development of biomarkers and their introduction into clinical routine practice. Recently a quality control program run by the Alzheimer's Association was started in order to harmonize procedures of laboratories world-wide. This program provides both standardized guide lines and external control CSF samples, and will allow longitudinal evaluation of laboratory performance.
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7.
  • Mattsson, Niklas, 1979, et al. (författare)
  • To know or not to know: ethical issues related to early diagnosis of Alzheimer's disease.
  • 2010
  • Ingår i: International journal of Alzheimer's disease. - : Hindawi Limited. - 2090-0252. ; 2010
  • Forskningsöversikt (refereegranskat)abstract
    • In Alzheimer's disease (AD), pathological processes start in the brain long before clinical dementia. Biomarkers reflecting brain alterations may therefore indicate disease at an early stage, enabling early diagnosis. This raises several ethical questions and the potential benefits of early diagnosis must be weighted against possible disadvantages. Currently, there are few strong arguments favouring early diagnosis, due to the lack of disease modifying therapy. Also, available diagnostic methods risk erroneous classifications, with potentially grave consequences. However, a possible benefit of early diagnosis even without disease modifying therapy is that it may enable early decision making when patients still have full decision competence, avoiding problems of hypothetical consents. It may also help identifying patients with cognitive dysfunction secondary to other diseases that may be responsive to treatment already today.
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8.
  • Portelius, Erik, 1977, et al. (författare)
  • Novel Aβ Isoforms in Alzheimer´s Disease - Their Role in Diagnosis and Treatment.
  • 2011
  • Ingår i: Current pharmaceutical design. - 1381-6128. ; 17:25, s. 2594-602
  • Forskningsöversikt (refereegranskat)abstract
    • The last decades have witnessed an explosion in studies of the role of amyloid-β (Aβ ) in the progress of the neurodegenerative disorder Alzheimer´s disease (AD) and it is now widely accepted that Aβ is related to the pathogenesis of AD. For example, studies have shown that Aβ is neurotoxic and that the neurotoxicity of Aβ is related to its aggregation state. The concentration of the 42 amino acid form of Aβ (Aβ 1-42) is reduced in the cerebrospinal fluid (CSF) from AD patients, which is believed to reflect the AD pathology with plaques in the brain acting as sinks. Less well investigated, however, is the ability of other Aβ isoforms to distinguish AD patients from controls and to identify treatment effects in clinical trials. Recently, novel C-truncated forms of Aβ (Aβ1-14, Aβ1-15, and Aβ1-16) were identified in human CSF. The presence of these small peptides is consistent with a catabolic amyloid precursor protein cleavage pathway by β- followed by α-secretase. It has been shown that Aβ1-14, Aβ1-15, and Aβ1-16 increase dose-dependently in response to γ-secretase inhibitor treatment while Aβ1-42 levels are unchanged. Here, we review the many aspects of Aβ and its isoforms with special focus on their potential role as diagnostic and theragnostic markers.
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9.
  • Schöll, Michael, 1980, et al. (författare)
  • Biomarkers for tau pathology.
  • 2019
  • Ingår i: Molecular and cellular neurosciences. - : Elsevier BV. - 1095-9327 .- 1044-7431. ; 97, s. 18-33
  • Forskningsöversikt (refereegranskat)abstract
    • The aggregation of fibrils of hyperphosphorylated and C-terminally truncated microtubule-associated tau protein characterizes 80% of all dementia disorders, the most common neurodegenerative disorders. These so-called tauopathies are hitherto not curable and their diagnosis, especially at early disease stages, has traditionally proven difficult. A keystone in the diagnosis of tauopathies was the development of methods to assess levels of tau protein in vivo in cerebrospinal fluid, which has significantly improved our knowledge about these conditions. Tau proteins have also been measured in blood, but the importance of tau-related changes in blood is still unclear. The recent addition of positron emission tomography ligands to visualize, map and quantify tau pathology has further contributed with information about the temporal and spatial characteristics of tau accumulation in the living brain. Together, the measurement of tau with fluid biomarkers and positron emission tomography constitutes the basis for a highly active field of research. This review describes the current state of biomarkers for tau biomarkers derived from neuroimaging and from the analysis of bodily fluids and their roles in the detection, diagnosis and prognosis of tau-associated neurodegenerative disorders, as well as their associations with neuropathological findings, and aims to provide a perspective on how these biomarkers might be employed prospectively in research and clinical settings.
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10.
  • Zetterberg, Henrik, 1973, et al. (författare)
  • Biochemical markers in Alzheimer's disease clinical trials.
  • 2010
  • Ingår i: Biomarkers in medicine. - 1752-0363. ; 4:1, s. 91-8
  • Forskningsöversikt (refereegranskat)abstract
    • This article summarizes how biochemical markers may aid in the development of novel treatments that interfere with fundamental pathogenic processes in Alzheimer's disease. Details are given on the potential use of biomarkers in Alzheimer's disease clinical trials as additional inclusion criteria to enrich study populations with participants who really suffer from the disease, as a means to stratify study participants into meaningful subgroups that may benefit differently from the treatment, and as tools to detect desired biochemical effects and undesired side effects of the drug.
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