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 their expression in relationship to clinical measurements of AD dementia progression.


METHODS
We measured inflammatory cytokine messenger RNA (mRNA) expression in postmortem brain specimens of elderly subjects at different clinical stages of dementia and neuropathological dysfunction.


METHODS
Postmortem study of nursing home patients.


RESULTS
In brains of cognitively normal control subjects, higher interleukin 6 (IL-6) and transforming growth factor beta1 (TGF-beta1) 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-beta1 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-beta1 mRNA did not correlate with the level of either neurofibrillary tangles or neuritic plaques. Interestingly, in the superior temporal gyrus, TGF-beta1 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. Arch Neurol. 2000;57:1153-1160
Neuroinflammation Research Laboratories, Department of Psychiatry, Box 1229, Mount Sinai Medical Center, One Gustave L Levy Place, New York, NY 10029, USA.
J D
JD
Luterman
V
V
Haroutunian
S
S
Yemul
L
L
Ho
D
D
Purohit
P S
PS
Aisen
R
R
Mohs
G M
GM
Pasinetti
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D003071:Cognition; D018450:Disease Progression; D018728:Entorhinal Cortex / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology; D009778:Occipital Lobe / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics*
D015850:Interleukin-6; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta