Longitudinal study of inflammatory factors in serum, cerebrospinalfluid, and brain tissue in Alzheimer disease: Interleukin-1 beta,interleukin-6, interleukin-1 receptor antagonist, tumor necrosisfactor-alpha, the soluble tumor necrosis factor receptors I and III,and alpha(1)-antichymotrypsin
A.S. Lanzrein
Bok Engelsk 1998
| Utgitt | 1998
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| Omfang | Side 215- 227
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| Opplysninger | There is evidence consistent with the hypothesis that inflammatoryand immune mechanisms are involved in the pathogenesis of Alzheimerdisease (AD). We have investigated whether the levels of inflammatoryassociated proteins in serum or lumbar cerebrospinal fluid (CSF)reflect the progressive cognitive decline and brain atrophy of AD-patients. Levels of interleukin-1 beta (IL-1 beta), IL-1 receptorantagonist (IL-1ra), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), the soluble TNF receptors type I and II (sTNFR Iand II), and the acute phase protein alpha(1)-antichymotrypsin(alpha(1)-ACT) were determined in paired serum and CSF samples takenyearly over a period of 2-5 years from pathologically confirmed ADpatients (n = 8) and normal controls or non-AD subjects with otherCNS pathology (n = 9). No significant differences were found betweenAD subjects and controls in the mean levels of the above mediators.There was also no correlation in either subject group between thelevels of these inflammatory mediators in serum or CSF, and thechange in cognitive status or the progression of the atrophy of themedial temporal lobe measured by X-ray computed tomography (CT). Theconcentrations of IL-1 beta, IL-6, and TNF-alpha were determined inbrain tissue specimens of five to nine different brain regions in sixof the AD patients and four of the lion-AD subjects. The levels of IL-1 beta and IL-6 in the various brain regions were not significantlydifferent in the AD and the non-AD group. However, in AD patients thelevel of TNF-alpha was significantly lower in the frontal cortex(32%, p = 0.024), the superior temporal gyrus (57%, p = 0.021), andthe entorhinal cortex (49%, p = 0.009) compared with non-AD subjects.Low levels of TNF-alpha in the brain areas that showed neuropathologyin AD may indicate a dysregulation of the inflammatory process in AD.Despite this finding, this study does not support the use ofmeasurements of any of the inflammatory mediators investigated hereas a diagnostic parameter for AD, due the large overlap in the levelsof these factors between AD patients and other subjects, and the poorrelation to clinical signs of AD.
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