Epidermal growth factor receptor expression in demented and aged human brain

Styren, Scot; Mufson, Elliot J.; Styren, Gisele C.; Civin, W. Harold; Rogers, Joseph

doi:10.1016/0006-8993(90)90647-t

Cited by 38 publications

(14 citation statements)

References 35 publications

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“…In AD brain, senile plaques are consistently found to 338 2 34 %s6 78 Pm contain and to be surrounded by reactive microglia [18][19][20]. Resident microglia are derived from immigrating monocytes which then undergo terminal maturation into resident microglia [18][19][20].…”

Section: Discussionmentioning

confidence: 99%

“…Resident microglia are derived from immigrating monocytes which then undergo terminal maturation into resident microglia [18][19][20]. This immigration occurs mainly in the perinatal period, but a low degree of immigration has been assumed to occur throughout life [18][19][20].…”

Section: Discussionmentioning

confidence: 99%

“…Three major APP protein forms of 695 [3], 751 [41, and 770 amino acids [5], respectively, are derived from an alternatively spliced hn mRNA. APP is synthesized in the brain as well as m several other organs and tissues of healthy individuals (for reviews, see [6,7]), Until now, only cortical and hippocampal neurons, astrocytes, and endothelial cells have been reported to be cortical sites of APP synthesis [5, 8-151. Although numerous reactiv~ microglia are consistently found in and around AD senile plaques [16][17][18][19] and although amyloid was found to beass0ciated with them [17,18,20] nothing is known so far as to whether this cell population of the brain may synthesize APP and thus may contribute to ,6A4 deposits, The question remained open whether the material was synthesized by the ceils themselves or whether it had been phagocytosed. Our intention was to obtain evidence whether or not human microglia might be able to express APP and how it may be regulated, We applied a previously described special cultivation system to obtain terminally Correspondettce address: J, Bauer', Psychiatrische Universit~tsklinik, Hauptstrasse 5, I3-7800 Freiburg, Germany.…”

Section: Introductionmentioning

confidence: 99%

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In‐vitro matured human macrophages express Alzheimer's βA4‐amyloid precursor protein indicating synthesis in microglial cells

Bauer

König²,

Strauss

et al. 1991

FEBS Letters

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Micr~tllia which are consistenlly associatad with Al~hoimer's disease {AD) );chile plaques ~tre part of the monontJcle:tr phailocyte system, ln.vltro mmured human monocyte.d©rived m;~crophaltcs rc~t,rc many immunological characteristics of microlilia. We found stronll conslJtutive ©xpr0ss~on of' Atxheimcr's//A4.mnyioid precursor protein (APP) in human mononuc|ear pim$ocytes after terminal in.vitro maturation from monoc2ctes to macrophalleS, Amyloid has previously been found to b0 ~s~i.nted wilh microgli~t in AD brains, however, it remained unclear whctl~er the material was synthesized in or had been phagocytoscd by the ceils, The flndinlts presented here support the ~|ssumption that brain mlcroglia may contribute to APP synthesis in AD brain, Macrophage: Micr<)lilia; Arnyloid pr~:ursor protein; AIzheinner'~ disease

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In‐vitro matured human macrophages express Alzheimer's βA4‐amyloid precursor protein indicating synthesis in microglial cells

Bauer

König²,

Strauss

et al. 1991

FEBS Letters

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“…We previously showed that EGFR immunoreactivity was localized to brain, pituitary and skin vascular endothelial cells of clinically diagnosed, pathologically confirmed AD patients. EGFR expression was also evident on blood vessels of patients with a variety of clinically diagnosed dementias (pathologically confirmed where possible) including Pick's disease, parkinsonian dementia and dementia of unknown origin [8,9]. In our cohort of living patients, EGFR expression does not correlate with clinical diagnosis of probable AD.…”

Section: Oooooooooooooooooooooomentioning

confidence: 73%

Epidermal Growth Factor Receptor Expression in Skin Does Not Predict Dementia in the Elderly

Styren¹,

Styren²,

DeKosky

1997

Dement Geriatr Cogn Disord

Self Cite

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We have previously reported that epidermal growth factor receptor (EGFR) was expressed on vascular endothelial cells from postmortem specimens of demented but not cognitively normal subjects. In the present study, we examined skin biopsies from 35 living patients who were either normal or had a clinical diagnosis of probable Alzheimer’s disease. In this living cohort, there was no correlation between the presence of vascular EGFR expression and clinically determined cognitive status. While a variety of factors may be responsible for these findings, endothelial EGFR expression cannot be used to confirm a premortem clinical diagnosis of dementia.

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“…SOCS-4 can be induced by epidermal growth factor (EGF) and regulates EGF receptor (EGFR) by competitively binding to phosphotyrosine sites with STAT3 (Bullock et al, 2007). Induction of EGFR expression in the vasculature and in neurons of AD brains has been observed (Styren et al, 1990;Ferrer et al, 1996). In addition, biomarker studies have shown increased levels of EGF in plasma of AD cases (Bjorkqvist et al, 2012;Marksteiner et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Expression of suppressor of cytokine signaling genes in human elderly and Alzheimer’s disease brains and human microglia

2015

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Multiple cellular systems exist to prevent uncontrolled inflammation in brain tissues; the Suppressor of cytokine signaling (SOCS) proteins have key roles in these processes. SOCS proteins are involved in restricting cellular signaling pathways by enhancing the degradation of activated receptors and removing the stimuli for continued activation. There are eight separate SOCS genes that code for proteins with similar structures and properties. All SOCS proteins can reduce signaling of activated transcription factors JAK and STAT, but they also regulate many other signaling pathways. SOCS-1 and SOCS-3 have particular roles in regulating inflammatory processes. Chronic inflammation is a key feature of the pathology present in Alzheimer’s disease (AD)-affected brains resulting from responses to amyloid plaques or neurofibrillary tangles, the pathological hallmarks of AD. The goal of this study was to examine SOCS gene expression in human non-demented (ND) and AD brains and in human brain-derived microglia to determine if AD-related pathology resulted in a deficit of these critical molecules. We demonstrated that SOCS-1, SOCS-2, SOCS-3 and CIS mRNA expression was increased in Aβ– and inflammatory-stimulated microglia, while SOCS-6 mRNA expression was decreased by both types of treatments. Using human brain samples from temporal cortex from ND and AD cases, SOCS-1 through SOCS-7 and CIS mRNA and SOCS-1 through SOCS-7 protein could be detected constitutively in ND and AD human brain samples. Although, the expression of key SOCS genes did not change to a large extent as a result of AD pathology, there were significantly increased levels of SOCS-2, SOCS-3 and CIS mRNA and increased protein levels of SOCS-4 and SOCS-7 in AD brains. In summary, there was no evidence of a deficit of these key inflammatory regulating proteins in aged or AD brains.

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Epidermal growth factor receptor expression in demented and aged human brain

Cited by 38 publications

References 35 publications

In‐vitro matured human macrophages express Alzheimer's βA4‐amyloid precursor protein indicating synthesis in microglial cells

In‐vitro matured human macrophages express Alzheimer's βA4‐amyloid precursor protein indicating synthesis in microglial cells

Epidermal Growth Factor Receptor Expression in Skin Does Not Predict Dementia in the Elderly

Expression of suppressor of cytokine signaling genes in human elderly and Alzheimer’s disease brains and human microglia

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