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

Abstract

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 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

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  • Authors+Show Affiliations

    ,

    Neuroinflammation Research Laboratories, Department of Psychiatry, Box 1229, Mount Sinai Medical Center, One Gustave L Levy Place, New York, NY 10029, USA.

    , , , , , ,

    Source

    Archives of neurology 57:8 2000 Aug pg 1153-60

    MeSH

    Aged
    Aged, 80 and over
    Alzheimer Disease
    Cognition
    Disease Progression
    Entorhinal Cortex
    Female
    Gene Expression
    Humans
    Interleukin-6
    Male
    Neurofibrillary Tangles
    Occipital Lobe
    Plaque, Amyloid
    RNA, Messenger
    Temporal Lobe
    Transforming Growth Factor beta

    Pub Type(s)

    Journal Article
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    10927795

    Citation

    Luterman, J D., et al. "Cytokine Gene Expression as a Function of the Clinical Progression of Alzheimer Disease Dementia." Archives of Neurology, vol. 57, no. 8, 2000, pp. 1153-60.
    Luterman JD, Haroutunian V, Yemul S, et al. Cytokine gene expression as a function of the clinical progression of Alzheimer disease dementia. Arch Neurol. 2000;57(8):1153-60.
    Luterman, J. D., Haroutunian, V., Yemul, S., Ho, L., Purohit, D., Aisen, P. S., ... Pasinetti, G. M. (2000). Cytokine gene expression as a function of the clinical progression of Alzheimer disease dementia. Archives of Neurology, 57(8), pp. 1153-60.
    Luterman JD, et al. Cytokine Gene Expression as a Function of the Clinical Progression of Alzheimer Disease Dementia. Arch Neurol. 2000;57(8):1153-60. PubMed PMID: 10927795.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Cytokine gene expression as a function of the clinical progression of Alzheimer disease dementia. AU - Luterman,J D, AU - Haroutunian,V, AU - Yemul,S, AU - Ho,L, AU - Purohit,D, AU - Aisen,P S, AU - Mohs,R, AU - Pasinetti,G M, PY - 2000/8/6/pubmed PY - 2000/9/9/medline PY - 2000/8/6/entrez SP - 1153 EP - 60 JF - Archives of neurology JO - Arch. Neurol. VL - 57 IS - 8 N2 - 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 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 SN - 0003-9942 UR - https://www.unboundmedicine.com/medline/citation/10927795/Cytokine_gene_expression_as_a_function_of_the_clinical_progression_of_Alzheimer_disease_dementia_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/vol/57/pg/1153 DB - PRIME DP - Unbound Medicine ER -