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

• Published in: Neurobiology of aging Vol. 31; no. 11; pp. 1877 - 1884
• Main Authors: Buchhave, Peder, Zetterberg, Henrik, Blennow, Kaj, Minthon, Lennart, Janciauskiene, Sabina, Hansson, Oskar
• Format: Journal Article
• Language: English
• Published: 01.11.2010
• Subjects: Aging
• ISSN: 0197-4580
• DOI: 10.1016/j.neurobiolaging.2008.10.012

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