ABSTRACT
A growing body of evidence points out the potential role of inflammatory mechanisms in the pathophysiology of brain damage in dementia. In previous studies, we have demonstrated intrathecal production of the proinflammatory cytokine tumor necrosis factor (TNF)alpha in patients with Alzheimer's disease (AD). The aim of the present study was to investigate the downstream products of TNF-alpha expression including interleukin (IL)1beta and its naturally occurring antagonist IL-1 receptor agonist (ra) in patients with AD. The cytokine levels were related to neuronal damage, as measured by intrathecal tau and beta-amyloid concentration and certain clinical features of the disease. Fifty-two patients with AD and 25 healthy controls were analyzed with respect to cerebrospinal fluid (CSF) levels of IL-1beta and IL-1ra. CSF IL-1beta was neither detectable in CSF of AD nor in control CSF. In contrast, a significantly lower (p < 0.01) number of patients (24 of 49) than of controls (20 of 24) showed detectable levels of IL-1ra in the CSF. The intrathecal levels of IL-1ra were significantly lower in patients with AD than in the controls. Our study demonstrates a decreased production of the anti-inflammatory compound IL-1ra, suggesting a propensity towards inflammation in patients with AD.
Subject(s)
Alzheimer Disease/cerebrospinal fluid , Sialoglycoproteins/cerebrospinal fluid , Aged , Aged, 80 and over , Amyloid beta-Peptides/cerebrospinal fluid , Cognition Disorders/cerebrospinal fluid , Enzyme-Linked Immunosorbent Assay , Female , Humans , Interleukin 1 Receptor Antagonist Protein , Male , Middle AgedABSTRACT
OBJECTIVE: To analyze the extent of tumor necrosis factor-alpha (TNFalpha) and TNFbeta gene polymorphism in patients with AD and to relate it to intrathecal levels of these cytokines. METHODS: Analyses of TNFalpha and TNFbeta gene polymorphism were performed using PCR in 52 patients with AD and in 25 control subjects, and the levels of corresponding cytokines were analyzed using ELISA. RESULTS: Patients with AD displayed significantly higher intrathecal levels of TNFalpha, but not TNFbeta, compared with the control subjects. The levels of these cytokines did not differ significantly in patients displaying different alleles of the TNF gene. CONCLUSIONS: Results indicate that increased intrathecal production of TNFalpha in AD is preferentially controlled by environmental stimuli rather than genetic makeup.