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Sökning: L773:1387 2877 OR L773:1875 8908

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  • Sun, Qiying, et al. (författare)
  • Increased Plasma TACE Activity in Subjects with Mild Cognitive Impairment and Patients with Alzheimer's Disease.
  • 2014
  • Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 41:3, s. 877-86
  • Tidskriftsartikel (refereegranskat)abstract
    • Evidence suggests that the tumor necrosis factor receptor (TNFR)-signaling pathway contributes to the pathogenesis of Alzheimer's disease (AD). TNF-α converting enzyme (TACE/ADAM-17) can cleave both pro-TNF-α and TNF receptors. Recently, we have shown that TACE activity in the cerebrospinal fluid (CSF) of subjects with mild cognitive impairment (MCI) and AD patients is significantly higher than that of cognitively healthy controls (HC). To date, it is not clear whether TACE activity could be detected in the human plasma and whether TACE activity in MCI and AD patients is different from that in HC. We analyzed TACE expression and activity in a large clinical sample of 64 patients with AD, 88 subjects with MCI, and 50 age-matched HC recruited from two distinct academic centers. Plasma TACE protein levels did not differ significantly in the three study groups (AD, MCI, and HC). However, plasma TACE activity in subjects with MCI and AD patients was significantly higher than that in HC. Moreover, in MCI and AD groups, we found a significant correlation between plasma TACE activity and CSF t-tau and Aβ42 levels and CSF Aβ42/tau ratios. In AD patients, the levels of plasma TACE activity correlated significantly and negatively with cognition. These findings further support the role of the TNF-α receptor complex in AD-related neuroinflammation and propose TACE plasma activity as a promising hypothesis-driven biomarker candidate for detection, diagnosis, and prognosis of prodromal and clinical AD.
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  • Svensson, Johan, 1964, et al. (författare)
  • Cerebrospinal Fluid Sulfatide Levels Lack Diagnostic Utility in the Subcortical Small Vessel Type of Dementia.
  • 2021
  • Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 82:2, s. 781-790
  • Tidskriftsartikel (refereegranskat)abstract
    • Sulfatides (STs) in cerebrospinal fluid (CSF), as well as magnetic resonance imaging (MRI)-detected white matter hyperintensities (WMHs), may reflect demyelination. Here, we investigated the diagnostic utility of CSF ST levels in the subcortical small vessel type of dementia (SSVD), which is characterized by the presence of brain WMHs.To study the diagnostic utility of CSF ST levels in SSVD.This was a mono-center, cross-sectional study of SSVD (n=16), Alzheimer's disease (n=40), mixed dementia (n=27), and healthy controls (n=33). Totally, 20 ST species were measured in CSF by liquid chromatography-mass spectrometry (LC-MS/MS).CSF total ST levels, as well as CSF levels of hydroxylated and nonhydroxylated ST species, did not differ across the study groups. In contrast, CSF neurofilament light chain (NFL) levels separated the patient groups from the controls. CSF total ST level correlated with CSF/serum albumin ratio in the total study population (r=0.64, p< 0.001) and in all individual study groups. Furthermore, CSF total ST level correlated positively with MRI-estimated WMH volume in the total study population (r=0.30, p< 0.05), but it did not correlate with CSF NFL level.Although there was some relation between CSF total ST level and WMH volume, CSF ST levels were unaltered in all dementia groups compared to the controls. This suggests that CSF total ST level is a poor biomarker of demyelination in SSVD. Further studies are needed to investigate the mechanisms underlying the marked correlation between CSF total ST level and CSF/serum albumin ratio.
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