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Sökning: L773:2090 0252

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1.
  • Andreasen, Niels, et al. (författare)
  • Neuroinflammation Screening in Immunotherapy Trials against Alzheimer's Disease.
  • 2010
  • Ingår i: International journal of Alzheimer's disease. - 2090-0252. ; :638379
  • Tidskriftsartikel (refereegranskat)abstract
    • Due to side effects in the form of meningoencephalitis in the interrupted phase II AN1792 trial of active antiamyloid β(Aβ) immunization against Alzheimer's disease (AD), there has been concern that anti-Aβ immunization may cause destructive neuroinflammation. Here, we report on two patients fulfilling clinical AD criteria who were diagnosed with Lyme neuroborreliosis during screening before inclusion in anti-Aβ immunotherapy trials. The two cases illustrate the necessity of careful biochemical screening for neuroinflammatory/neuroinfectious conditions before an AD diagnosis is made and before clinical AD patients are included in trials of therapy that could impact the immune system. Should the two cases have been included and deteriorated, additional investigations might have led to the erroneous conclusion that therapy-induced meningoencephalitis had occurred.
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2.
  • Bjerke, Maria, et al. (författare)
  • Confounding factors influencing amyloid Beta concentration in cerebrospinal fluid.
  • 2010
  • Ingår i: International journal of Alzheimer's disease. - 2090-0252. ; 2010
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Patients afflicted with Alzheimer's disease (AD) exhibit a decrease in the cerebrospinal fluid (CSF) concentration of the 42 amino acid form of beta-amyloid (Abeta(42)). However, a high discrepancy between different centers in measured Abeta(42) levels reduces the utility of this biomarker as a diagnostic tool and in monitoring the effect of disease modifying drugs. Preanalytical and analytical confounding factors were examined with respect to their effect on the measured Abeta(42) level. Methods. Aliquots of CSF samples were either treated differently prior to Abeta(42) measurement or analyzed using different commercially available xMAP or ELISA assays. Results. Confounding factors affecting CSF Abeta(42) levels were storage in different types of test tubes, dilution with detergent-containing buffer, plasma contamination, heat treatment, and the origin of the immunoassays used for quantification. Conclusion. In order to conduct multicenter studies, a standardized protocol to minimize preanalytical and analytical confounding factors is warranted.
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3.
  • Blom, Elin S, et al. (författare)
  • Increased mRNA Levels of TCF7L2 and MYC of the Wnt Pathway in Tg-ArcSwe Mice and Alzheimer's Disease Brain
  • 2010
  • Ingår i: International journal of Alzheimer's disease. - 2090-0252. ; 2011, s. 936580
  • Tidskriftsartikel (refereegranskat)abstract
    • Several components in the Wnt pathway, including β-catenin and glycogen synthase kinase 3 beta, have been implied in AD pathogenesis. Here, mRNA brain levels from five-month-old tg-ArcSwe and nontransgenic mice were compared using Affymetrix microarray analysis. With surprisingly small overall changes, Wnt signaling was the most affected pathway with altered expression of nine genes in tg-ArcSwe mice. When analyzing mRNA levels of these genes in human brain, transcription factor 7-like 2 (TCF7L2) and v-myc myelocytomatosis viral oncogene homolog (MYC), were increased in Alzheimer's disease (AD) (P < .05). Furthermore, no clear differences in TCF7L2 and MYC mRNA were found in brains with frontotemporal lobar degeneration, suggesting that altered regulation of these Wnt-related genes could be specific to AD. Finally, mRNA levels of three neurogenesis markers were analyzed. Increased mRNA levels of dihydropyrimidinase-like 3 were observed in AD brain, suggesting that altered Wnt pathway regulation may signify synaptic rearrangement or neurogenesis.
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4.
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5.
  • Gustafson, Lars, et al. (författare)
  • A factor analytic approach to symptom patterns in dementia.
  • 2010
  • Ingår i: International journal of Alzheimer's disease. - 2090-0252.
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous publications have shown a high diagnostic sensitivity and specificity of three short clinical rating scales for Alzheimer's disease (AD), frontotemporal dementia (FTD), and vascular dementia (VaD) validated against neuropathological (NP) diagnoses. In this study, the aim was to perform an exploratory factor analysis of the items in these clinical rating scales. The study included 190 patients with postmortem diagnoses of AD (n = 74), VaD (n = 33), mixed AD/VaD (n = 31), or FTD (n = 52). The factor analysis produced three strong factors. Factor 1 contained items describing cerebrovascular disease, similar to the Hachinski Ischemic Score. Factor 2 enclosed major clinical characteristics of FTD, and factor 3 showed a striking similarity to the AD scale. A fourth symptom cluster was described by perception and expression of emotions. The factor analyses strongly support the construct validity of the diagnostic rating scales.
6.
  • Lautner, Ronald, et al. (författare)
  • Biomarkers for microglial activation in Alzheimer's disease.
  • 2011
  • Ingår i: International journal of Alzheimer's disease. - 2090-0252. ; 2011
  • Tidskriftsartikel (refereegranskat)abstract
    • Intensive research over the last decades has provided increasing evidence for neuroinflammation as an integral part in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD). Inflammatory responses in the central nervous system (CNS) are initiated by activated microglia, representing the first line of the innate immune defence of the brain. Therefore, biochemical markers of microglial activation may help us understand the underlying mechanisms of neuroinflammation in AD as well as the double-sided qualities of microglia, namely, neuroprotection and neurotoxicity. In this paper we summarize candidate biomarkers of microglial activation in AD along with a survey of recent neuroimaging techniques.
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7.
  • 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. - 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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8.
  • 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. - 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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9.
  • Mulugeta, Ezra, et al. (författare)
  • Cerebrospinal Fluid Levels of sAPPα and sAPPβ in Lewy Body and Alzheimer's Disease: Clinical and Neurochemical Correlates.
  • 2011
  • Ingår i: International journal of Alzheimer's disease. - 2090-0252. ; 2011
  • Tidskriftsartikel (refereegranskat)abstract
    • We measured cerebrospinal fluid (CSF) levels of the soluble isoforms of amyloid precursor protein (APP; sAPPα sAPPβ) and other CSF biomarkers in 107 patients with Alzheimer's disease (AD), dementia with Lewy body dementia (DLB), Parkinson's disease dementia (PDD), and normal controls (NC) using commercial kits. DLB and PDD were combined in a Lewy body dementia group (LBD). No differences were observed in sAPPα and sAPPβ levels between the groups. Significant correlations were observed between sAPPα and sAPPβ and between sAPPβ and Mini-Mental State Examination scores in the total group analysis as well as when LBD and AD groups were analyzed separately. sAPPα and sAPPβ levels correlated with Aβ38, Aβ40, Aβ42, and Tau in the LBD group. In AD, sAPPα correlated with p-Tau and sAPPβ with Aβ40. The differential association between sAPPα and sAPPβ with Aβ and Tau species between LBD and AD groups suggests a possible relationship with the underlying pathologies in LBD and AD.
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10.
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