Soluble TNF receptors are associated with Aß metabolism and conversion to dementia in subjects with mild cognitive impairment.
Neurobiol Aging
; 31(11): 1877-84, 2010 Nov.
Article
in En
| MEDLINE
| ID: mdl-19070941
ABSTRACT
OBJECTIVE:
There is evidence supporting that tumor necrosis factor receptor (TNFR)-signaling can induce production of beta-amyloid (Aß) 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 ß-site APP-cleaving enzyme 1 (BACE1) activity (r(s)=0.53-0.68, p<0.01) and Aß 40 levels (r(s)=0.59-0.71, p<0.001). Similarly, both sTNFRs were associated with Aß 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dementia, Vascular
/
Amyloid beta-Peptides
/
Cognition Disorders
/
Receptors, Tumor Necrosis Factor, Type I
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Receptors, Tumor Necrosis Factor, Type II
/
Alzheimer Disease
Type of study:
Observational_studies
/
Risk_factors_studies
Limits:
Aged
/
Aged80
/
Female
/
Humans
/
Male
Language:
En
Journal:
Neurobiol Aging
Year:
2010
Document type:
Article
Affiliation country: