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

Buchhave, Peder LU ; Zetterberg, Henrik; Blennow, Kaj; Minthon, Lennart LU ; Janciauskiene, Sabina LU and Hansson, Oskar LU (2010) In Neurobiology of Aging 31(11). p.1877-1884
Abstract
OBJECTIVE: There is evidence supporting that tumor necrosis factor receptor (TNFR)-signaling can induce production of beta-amyloid (Abeta) 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... (More)
OBJECTIVE: There is evidence supporting that tumor necrosis factor receptor (TNFR)-signaling can induce production of beta-amyloid (Abeta) 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 Abeta 40 levels (r(s)=0.59-0.71, p<0.001). Similarly, both sTNFRs were associated with Abeta 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
beta-Amyloid, Tumor necrosis factor receptor, TNF, Tumor necrosis factor, Alzheimer's disease, Mild cognitive impairment
in
Neurobiology of Aging
volume
31
issue
11
pages
1877 - 1884
publisher
Elsevier
external identifiers
  • wos:000282907800005
  • pmid:19070941
  • scopus:77956933314
ISSN
1558-1497
DOI
10.1016/j.neurobiolaging.2008.10.012
language
English
LU publication?
yes
id
c4c0c9cf-29dc-47a6-a609-13577f1689bd (old id 1276268)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19070941?dopt=Abstract
date added to LUP
2009-01-09 11:11:25
date last changed
2018-07-01 03:08:44
@article{c4c0c9cf-29dc-47a6-a609-13577f1689bd,
  abstract     = {OBJECTIVE: There is evidence supporting that tumor necrosis factor receptor (TNFR)-signaling can induce production of beta-amyloid (Abeta) 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&lt;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&lt;0.01) and Abeta 40 levels (r(s)=0.59-0.71, p&lt;0.001). Similarly, both sTNFRs were associated with Abeta 40 (r(s)=0.39-0.46, p&lt;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&lt;0.001). CONCLUSION: TNFR-signaling might be involved in the early pathogenesis of AD and VaD, and could be associated with beta-amyloid metabolism.},
  author       = {Buchhave, Peder and Zetterberg, Henrik and Blennow, Kaj and Minthon, Lennart and Janciauskiene, Sabina and Hansson, Oskar},
  issn         = {1558-1497},
  keyword      = {beta-Amyloid,Tumor necrosis factor receptor,TNF,Tumor necrosis factor,Alzheimer's disease,Mild cognitive impairment},
  language     = {eng},
  number       = {11},
  pages        = {1877--1884},
  publisher    = {Elsevier},
  series       = {Neurobiology of Aging},
  title        = {Soluble TNF receptors are associated with Abeta metabolism and conversion to dementia in subjects with mild cognitive impairment.},
  url          = {http://dx.doi.org/10.1016/j.neurobiolaging.2008.10.012},
  volume       = {31},
  year         = {2010},
}