Intracerebral production of tumor necrosis factor-alpha, a local neuroprotective agent, in Alzheimer disease and vascular dementia - PubMed (original) (raw)
Intracerebral production of tumor necrosis factor-alpha, a local neuroprotective agent, in Alzheimer disease and vascular dementia
E Tarkowski et al. J Clin Immunol. 1999 Jul.
Abstract
The local pattern of proinflammatory cytokine release was studied in Alzheimer disease (AD) and vascular dementia (VAD), by measuring intrathecal levels of IL-1 beta, IL-6, TNF-alpha, and its naturally occurring antagonists, soluble TNF receptors I and II. The cytokine levels were related to neuronal damage, as measured by the intrathecal tau concentration, to cerebral apoptosis assessed by levels of Fas/APO-1 and bcl-2, and to clinical variables. In vitro analysis was performed to study the effect of TNF-alpha on the production of bcl-2, an antiapoptotic factor, by human neuronal cells. Patients with both AD and VAD displayed significantly higher intrathecal levels of TNF-alpha compared to controls. In addition, patients with AD showed significantly negative correlations between the intrathecal levels of TNF-alpha and the levels of Fas/APO-1 as well as of tau protein. The level of bcl-2 in supernatants of TNF-alpha-exposed cultures of human neuronal cells was up to three times higher than in control supernatants. Our study demonstrates intrathecal production of TNF-alpha in patients with dementias, suggesting that this cytokine may have a neuroprotective role in these neurodegenerative conditions as evidenced by negative correlations between this cytokine and (i) levels of intrathecal Fas/APO-1 and (ii) levels of tau protein, both parameters closely related to brain damage. Our in vitro data suggest that TNF-alpha exerts its neuroprotective effect by stimulating neuronal cells to express bcl-2, a molecule which downregulates apoptosis.
Similar articles
- Intrathecal expression of proteins regulating apoptosis in acute stroke.
Tarkowski E, Rosengren L, Blomstrand C, Jensen C, Ekholm S, Tarkowski A. Tarkowski E, et al. Stroke. 1999 Feb;30(2):321-7. doi: 10.1161/01.str.30.2.321. Stroke. 1999. PMID: 9933267 - Cerebral pattern of pro- and anti-inflammatory cytokines in dementias.
Tarkowski E, Liljeroth AM, Minthon L, Tarkowski A, Wallin A, Blennow K. Tarkowski E, et al. Brain Res Bull. 2003 Aug 15;61(3):255-60. doi: 10.1016/s0361-9230(03)00088-1. Brain Res Bull. 2003. PMID: 12909295 Review. - Longitudinal study of inflammatory factors in serum, cerebrospinal fluid, and brain tissue in Alzheimer disease: interleukin-1beta, interleukin-6, interleukin-1 receptor antagonist, tumor necrosis factor-alpha, the soluble tumor necrosis factor receptors I and II, and alpha1-antichymotrypsin.
Lanzrein AS, Johnston CM, Perry VH, Jobst KA, King EM, Smith AD. Lanzrein AS, et al. Alzheimer Dis Assoc Disord. 1998 Sep;12(3):215-27. doi: 10.1097/00002093-199809000-00016. Alzheimer Dis Assoc Disord. 1998. PMID: 9772027 - Correlation between intrathecal sulfatide and TNF-alpha levels in patients with vascular dementia.
Tarkowski E, Tullberg M, Fredman P, Wikkelsö C. Tarkowski E, et al. Dement Geriatr Cogn Disord. 2003;15(4):207-11. doi: 10.1159/000068780. Dement Geriatr Cogn Disord. 2003. PMID: 12626853 - Impaired autophagy and APP processing in Alzheimer's disease: The potential role of Beclin 1 interactome.
Salminen A, Kaarniranta K, Kauppinen A, Ojala J, Haapasalo A, Soininen H, Hiltunen M. Salminen A, et al. Prog Neurobiol. 2013 Jul-Aug;106-107:33-54. doi: 10.1016/j.pneurobio.2013.06.002. Epub 2013 Jul 1. Prog Neurobiol. 2013. PMID: 23827971 Review.
Cited by
- In a circuit necessary for cognition and emotional affect, Alzheimer's-like pathology associates with neuroinflammation, cognitive and motivational deficits in the young adult TgF344-AD rat.
Hernandez CM, McCuiston MA, Davis K, Halls Y, Carcamo Dal Zotto JP, Jackson NL, Dobrunz LE, King PH, McMahon LL. Hernandez CM, et al. Brain Behav Immun Health. 2024 Jun 6;39:100798. doi: 10.1016/j.bbih.2024.100798. eCollection 2024 Aug. Brain Behav Immun Health. 2024. PMID: 39022628 Free PMC article. - Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer's disease mice.
Jagadeesan N, Roules GC, Chandrashekar DV, Yang J, Kolluru S, Sumbria RK. Jagadeesan N, et al. J Transl Med. 2024 Mar 18;22(1):291. doi: 10.1186/s12967-024-05008-x. J Transl Med. 2024. PMID: 38500108 Free PMC article. - Early Diagnosis of Alzheimer's Disease with Blood Test; Tempting but Challenging.
Farvadi F, Hashemi F, Amini A, Alsadat Vakilinezhad M, Raee MJ. Farvadi F, et al. Int J Mol Cell Med. 2023;12(2):172-210. doi: 10.22088/IJMCM.BUMS.12.2.172. Int J Mol Cell Med. 2023. PMID: 38313372 Free PMC article. Review. - Association between dementia risk and ulcerative colitis, with and without colectomy: a Swedish population-based register study.
Garcia-Argibay M, Hiyoshi A, Montgomery S. Garcia-Argibay M, et al. BMJ Open. 2023 Dec 22;13(12):e074110. doi: 10.1136/bmjopen-2023-074110. BMJ Open. 2023. PMID: 38135306 Free PMC article. - Molecular biomarkers for vascular cognitive impairment and dementia.
Hosoki S, Hansra GK, Jayasena T, Poljak A, Mather KA, Catts VS, Rust R, Sagare A, Kovacic JC, Brodtmann A, Wallin A, Zlokovic BV, Ihara M, Sachdev PS. Hosoki S, et al. Nat Rev Neurol. 2023 Dec;19(12):737-753. doi: 10.1038/s41582-023-00884-1. Epub 2023 Nov 13. Nat Rev Neurol. 2023. PMID: 37957261 Review.
References
- Clin Exp Immunol. 1997 Dec;110(3):492-9 - PubMed
- Exp Neurol. 1994 Feb;125(2):286-95 - PubMed
- J Neurosci. 1996 Dec 1;16(23):7533-9 - PubMed
- Proc Natl Acad Sci U S A. 1989 Oct;86(19):7611-5 - PubMed
- J Neurochem. 1992 Feb;58(2):454-60 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous