Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Nov;31(11):1877-84.
doi: 10.1016/j.neurobiolaging.2008.10.012. Epub 2008 Dec 13.

Soluble TNF Receptors Are Associated With Aβ Metabolism and Conversion to Dementia in Subjects With Mild Cognitive Impairment

Affiliations

Soluble TNF Receptors Are Associated With Aβ Metabolism and Conversion to Dementia in Subjects With Mild Cognitive Impairment

Peder Buchhave et al. Neurobiol Aging. .

Abstract

Objective: There is evidence supporting that tumor necrosis factor receptor (TNFR)-signaling can induce production of beta-amyloid (Aβ) 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 β-site APP-cleaving enzyme 1 (BACE1) activity (r(s)=0.53-0.68, p<0.01) and Aβ 40 levels (r(s)=0.59-0.71, p<0.001). Similarly, both sTNFRs were associated with Aβ 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.

Similar articles

See all similar articles

Cited by 39 articles

See all "Cited by" articles

Publication types

MeSH terms

Substances

LinkOut - more resources

Feedback