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James D. Luterman, PhD; Vahram Haroutunian, PhD; Shrishailam Yemul, PhD; Lap Ho, PhD; Dushyant Purohit, MD; Paul S. Aisen, MD; Richard Mohs, MD; Giulio Maria Pasinetti, MD, PhD

Arch Neurol. 2000;57:1153-1160.

Background  Inflammatory cytokines have been linked to Alzheimer disease (AD) neurodegeneration, but little is known about the temporal control of their expression in relationship to clinical measurements of AD dementia progression.

Design and Main Outcome Measures  We measured inflammatory cytokine messenger 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 interleukin 6 (IL-6) and transforming growth factor 1 (TGF-1) mRNA expression was observed in the entorhinal cortex and superior temporal gyrus compared 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-1 mRNA expression in the entorhinal cortex (P<.01) and superior temporal gyrus (P<.01). When stratified by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropathological criteria, IL-6 mRNA expression in both the entorhinal cortex (P<.05) and superior temporal gyrus (P<.01) correlated with the level of neurofibrillary tangles but not neuritic plaques. However, in the entorhinal cortex, TGF-1 mRNA did not correlate with the level of either neurofibrillary tangles or neuritic plaques. Interestingly, in the superior temporal gyrus, TGF-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 expression may differentially contribute to the vulnerability of independent cortical regions during the clinical progression of AD and suggest that an inflammatory cytokine response to the pathological effects of AD does not occur until the late stages of the disease. These findings have implications for the design of anti-inflammatory treatment strategies.

From the Neuroinflammation Research Laboratories, Department of Psychiatry (Drs Luterman, Yemul, Ho, and Pasinetti), Department of Pathology (Dr Purohit), and Psychiatry (Dr Mohs), Mount Sinai School of Medicine, New York, NY; Department of Psychiatry, Bronx Veterans Affairs Medical Center, Bronx, NY (Dr Haroutunain); and Department of Neurology, Georgetown University School of Medicine, Washington, DC (Dr Aisen).

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