Inflammatory Markers in Matched Plasma and Cerebrospinal Fluid from Patients with Alzheimer’s Disease

Department of Medicine, Malmö University Hospital, Malmö, Sweden.
Dementia and Geriatric Cognitive Disorders (Impact Factor: 3.55). 07/2003; 16(3):136-44. DOI: 10.1159/000071001
Source: PubMed


It has been suggested that a number of molecules associated with inflammation are involved in the pathogenesis of Alzheimer's disease (AD). We measured the levels of alpha(1)-antichymotrypsin (ACT), alpha(1)-antitrypsin (AAT), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and oxidised low-density lipoprotein (oxLDL) in matched cerebrospinal fluid (CSF) and plasma of 141 patients with probable AD. We found a significant relationship between CSF and plasma levels of ACT (r = 0.4, p < 0.001), IL-6 (r = 0.74, p < 0.001), MCP-1 (r = 0.71, p < 0.001), and a borderline relationship between CSF and plasma oxLDL (r = 0.22, p < 0.05). In addition, linear regression analysis revealed a positive correlation between levels of CSF-ACT and oxLDL (p < 0.001), but an inverse relation between levels of CSF ACT, CSF AAT and MCP-1 (p < 0.001). A significant correlation was also found between levels of CSF ACT, oxLDL and the ratio of CSF to serum albumin, which is used as a measure of the blood-brain barrier function. Our data extend previous reports regarding the inflammatory markers in the plasma and CSF of patients with AD and provide good evidence that levels of ACT, IL-6, MCP-1 and oxLDL in plasma and CSF might be candidates as biomarkers for monitoring the inflammatory process in AD.

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    • "The involvement of cytokines in AD is inferred from several changes in their concentrations in both CSF and plasma [35,36]. Although whether certain biomarkers from the brain enter the circulation or vice versa is still debated, either microglia or other peripheral cells produce and secrete a wide range of cytokines and chemokines [37]. Circulating cytokines have short half-lives, they may reach high concentrations at the sites of release and much lower concentrations after dilution in blood, and they may circulate bound to molecules that can prevent their detection by immunological methods [38]. "
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    ABSTRACT: Multiple pathogenic factors may contribute to the pathophysiology of Alzheimer's disease (AD). Peripheral blood markers have been used to assess biochemical changes associated with AD and mild cognitive impairment (MCI) and involved in their pathophysiology. Plasma samples and clinical data were obtained from participants in the Ansan Geriatric Study (AGE study). Plasma concentrations of four candidate biomarkers were measured in the normal control (NC), MCI, and AD group: interleukin-8 (IL-8), IL-10, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α).Body mass index (BMI), MMSE (Mini Mental State Examination), CDR(Clinical Dementia Rating) score and homocystein level were recorded with social and demographic information. Total of 59 subjects were randomly selected for this analysis [NC (n = 21), MCI(n = 20) and AD(n = 18)]. In demographic data, educational year was correlated with the diagnosis states (p < 0.0001). No significant differences in cardiovascular disease, BMI and use of NSAIDs were found in MCI or AD group compared with NC group, respectively. The involvement of inflammatory illness or conditions in subjects, WBC count, fibrinogen and homocystein of the three groups, but no significant differences were found in each groups. The plasma IL-8 level was lower in MCI and AD patients compared with the normal control group (respectively, p < 0.0001). The MCI and AD patients had similar MCP-1, IL-10, and TNF-α level. Our study suggests the existence of an independent and negative relationship between plasma IL-8 levels and functional status in MCI and AD patients.
    BMC Neurology 05/2011; 11(1):51. DOI:10.1186/1471-2377-11-51 · 2.04 Impact Factor
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    • "For none of these proteins does conclusive data exist that there is a correlation with these markers and the severity of the disease. [262] [263] [264] [265] [266] [267] [268] [269] In summary the available data shows, that A␤ 1-42 , t-tau and p-tau are valuable markers which support the clinical diagnosis of Alzheimer's disease. However, these markers are not sensitive to disease progression and cannot be used to monitor the severity of Alzheimer's disease. "
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    ABSTRACT: Older persons with Mild Cognitive Impairment (MCI) feature neurobiological Alzheimer's Disease (AD) in 50% to 70% of the cases and develop dementia within the next 5 to 7 years. Current evidence suggests that biochemical, neuroimaging, electrophysiological, and neuropsychological markers can track the disease over time since the MCI stage (also called prodromal AD). The amount of evidence supporting their validity is of variable strength. We have reviewed the current literature and categorized evidence of validity into three classes: Class A, availability of multiple serial studies; Class B a single serial study or multiple cross sectional studies of patients with increasing disease severity from MCI to probable AD; and class C, multiple cross sectional studies of patients in the dementia stage, not including the MCI stage. Several Class A studies suggest that episodic memory and semantic fluency are the most reliable neuropsychological markers of progression. Hippocampal atrophy, ventricular volume and whole brain atrophy are structural MRI markers with class A evidence. Resting-state fMRI and connectivity, and diffusion MR markers in the medial temporal white matter (parahippocampus and posterior cingulum) and hippocampus are promising but require further validation. Change in amyloid load in MCI patients warrant further investigations, e.g. over longer period of time, to assess its value as marker of disease progression. Several spectral markers of resting state EEG rhythms that might reflect neurodegenerative processes in the prodromal stage of AD (EEG power density, functional coupling, spectral coherence, and synchronization) suffer from lack of appropriately designed studies. Although serial studies on late event-related potentials (ERPs) in healthy elders or MCI patients are inconclusive, others tracking disease progression and effects of cholinesterase inhibiting drugs in AD, and cross-sectional including MCI or predicting development of AD offer preliminary evidence of validity as a marker of disease progression from the MCI stage. CSF Markers, such as Aβ 1-42, t-tau and p-tau are valuable markers which support the clinical diagnosis of Alzheimer's disease. However, these markers are not sensitive to disease progression and cannot be used to monitor the severity of Alzheimer's disease. For Isoprostane F2 some evidence exists that its increase correlates with the progression and the severity of AD.
    Journal of Alzheimer's disease: JAD 01/2011; 26 Suppl 3:159-99. DOI:10.3233/JAD-2011-0043 · 4.15 Impact Factor
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    • "The number of activated astrocytes is increased in AD and these are associated with senile plaques and with cerebral microvessels (Cullen et al. 1997). In the hippocampus of AD patients, there is an up-regulation of proinflammatory genes (Colangelo et al., 2002), and levels of cytokines are elevated in the brain (Zhao et al., 2003) as well as cerebrospinal fluid and plasma (Sun et al., 2003) of AD patients. Such age-related increased neuroinflammation has adverse consequences in that the brain is sensitized to the effects of infection or stress (Sparkman and Johnson, 2008). "
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    ABSTRACT: Evidence for the neurotoxicity of extended exposure to low levels of aluminum salts is described using an animal model treated with aluminum at low levels reflecting those found in some water supplies. Emphasis is given to the potential role of aluminum in acceleration and promotion of some indices characteristic of brain aging. These hallmarks include the appearance of excess levels of inflammation in specific brain areas. Aluminum salts can increase levels of glial activation, inflammatory cytokines and amyloid precursor protein within the brain. Both normal brain aging and to a greater extent, Alzheimer's disease are associated with elevated basal levels of markers for inflammation. These are not attributable to obvious exogenous stimuli and may reflect the lifespan history of the organism's immune responses. It is possible that aluminum salts can act as a subtle promoter of such apparently unprovoked responses.
    NeuroToxicology 09/2010; 31(5):575-81. DOI:10.1016/j.neuro.2010.05.009 · 3.38 Impact Factor
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