Cytokine gene expression as a function of the clinical progression of Alzheimer disease dementia

Background Inflammatory cytokines have been linked to Alzheimer disease (AD ) neurodegeneration, but little is known about the temporal control of thei r expression in relationship to clinical measurements of AD dementia progre ssion. Design and Main Outcome Measures: We measured inflammatory cytokine messeng er RNA (mRNA) expression in postmortem brain specimens of elderly subjects at different clinical stages of dementia and neuropathological dysfunction. Setting and Patients: Postmortem study of nursing home patients. Results: In brains of cognitively normal control subjects, higher interleuk in 6 (IL-6) and transforming growth factor beta 1 (TGF-beta 1) mRNA express ion was observed in the entorhinal cortex and superior temporal gyrus compa red with the occipital cortex. Compared with age-matched controls, subjects with severe/terminal dementia, but not subjects at earlier disease stages, had higher IL-6 and TGF-beta 1 mRNA expression in the entorhinal cortex (P <.01) and superior temporal gyrus (P<.01). When stratified by the Consortiu m to Establish a Registry for Alzheimer's Disease (CERAD) neuropathological criteria, IL-6 mRNA expression in both the entorhinal cortex (P<.05) and s uperior temporal gyrus (P<.01) correlated with the level of neurofibrillary tangles but not neuritic plaques. However, in the entorhinal cortex, TGF-b eta 1 mRNA did not correlate with the level of either neurofibrillary tangl es or neuritic plaques. Interestingly, in the superior temporal gyrus, TGF- beta 1 mRNA expression negatively correlated with neurofibrillary tangles ( P<.01) and showed no relationship to the pathological features of neuritic plaques. Conclusions: The data are consistent with the hypothesis that cytokine expr ession may differentially contribute to the vulnerability of independent co rtical regions during the clinical progression of AD and suggest that an in flammatory cytokine response to the pathological effects of AD does not occ ur until the late stages of the disease. These findings have implications f or the design of anti-inflammatory treatment strategies.