Soluble TNF receptors are associated with Aβ metabolism and conversion to dementia in subjects with mild cognitive impairment

被引:91
作者
Buchhave, Peder [1 ,2 ]
Zetterberg, Henrik [3 ,4 ]
Blennow, Kaj [3 ,4 ]
Minthon, Lennart [1 ,2 ]
Janciauskiene, Sabina [5 ]
Hansson, Oskar [1 ,2 ]
机构
[1] Malmo Univ Hosp, Neuropsychiat Clin, SE-20502 Malmo, Sweden
[2] Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, S-22100 Lund, Sweden
[3] Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Neurosci & Physiol, Dept Neurochem & Psychiat, Gothenburg, Sweden
[4] Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Biomed, Dept Clin Chem & Transfus Med, Gothenburg, Sweden
[5] Malmo Univ Hosp, Dept Clin Sci, SE-20502 Malmo, Sweden
基金
瑞典研究理事会;
关键词
Mild cognitive impairment; Alzheimer's disease; Tumor necrosis factor; TNF; Tumor necrosis factor receptor; beta-Amyloid; TUMOR-NECROSIS-FACTOR; ALZHEIMERS-DISEASE PATIENTS; VASCULAR DEMENTIA; CEREBROSPINAL-FLUID; FACTOR-ALPHA; INTRACEREBRAL PRODUCTION; INTERFERON-GAMMA; FACTOR DEATH; PROTEIN; BRAIN;
D O I
10.1016/j.neurobiolaging.2008.10.012
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Objective: There is evidence supporting that tumor necrosis factor receptor (TNFR)-signaling can induce production of beta-amyloid (A beta) in the brain. Moreover, amyloid-induced toxicity has been shown to be dependent on TNFR-signaling. However, it is still unclear whether TNFRs are involved in the early stages of dementia. Methods: We analyzed soluble TNFR1 and TNFR2 levels in plasma and cerebrospinal fluid (CSF) at baseline in 137 patients with mild cognitive impairment (MCI) and 30 age-matched controls. The MCI patients were followed for 4-6 years with an incidence of Alzheimer's disease (AD) or vascular dementia (VaD) of 15% per year. Results: The patients with MCI who subsequently developed these forms of dementias had higher levels of sTNFR1 and sTNFR2 in both CSF and plasma already at baseline when compared to age-matched controls (p < 0.05). In the CSF of MCI subjects and controls the levels of both sTNFR1 and sTNFR2 correlated strongly with beta-site APP-cleaving enzyme 1 (BACE1) activity (r(s) = 0.53-0.68, p < 0.01) and A beta. 40 levels (r(s) = 0.59-0.71, p < 0.001). Similarly, both sTNFRs were associated with A beta 40 (r(s) = 0.39-0.46, p < 0.05) in plasma. Finally, the levels of both sTNFRs correlated with the axonal damage marker tau in the CSF of MCI subjects and controls (r(s) = 0.57-0.83, p < 0.001). Conclusion: TNFR-signaling might be involved in the early pathogenesis of AD and VaD, and could be associated with beta-amyloid metabolism. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:1877 / 1884
页数:8
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