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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1276268
- author
- Buchhave, Peder
LU
; Zetterberg, Henrik
; Blennow, Kaj
; Minthon, Lennart
LU
; Janciauskiene, Sabina
LU
and Hansson, Oskar
LU
- organization
- publishing date
- 2010
- 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
- pmid:19070941
- 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
- 2016-04-01 10:13:30
- date last changed
- 2022-05-17 21:00:34
@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<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.}},
author = {{Buchhave, Peder and Zetterberg, Henrik and Blennow, Kaj and Minthon, Lennart and Janciauskiene, Sabina and Hansson, Oskar}},
issn = {{1558-1497}},
keywords = {{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}},
doi = {{10.1016/j.neurobiolaging.2008.10.012}},
volume = {{31}},
year = {{2010}},
}