Welcome to the INR Blog

Welcome to the INR Blog!

This Blog is still in development. The aim of this blog is to add further scientific information to the content of the INR website as soon as it becomes available. If possible in the future postings and comments from website visitors will be enabled. Thank you for your interest.

Edward Tobinick MD

Recent published research results:

Anti-TNF-alpha reduces amyloid plaques and tau phosphorylation and induces CD11c-positive dendritic-like cell in the APP/PS1 transgenic mouse brains. Shi JQ, Shen W, Chen J, Wang BR, Zhong LL, Zhu YW, Zhu HQ, Zhang QQ, Zhang YD, Xu J. Brain Res. 2010 Oct 21.
Inflammation plays an important role in the pathogenesis of Alzheimer’s disease (AD). Overexpression of tumor necrosis factor-alpha (TNF-alpha) occurs in the AD brain. Recent clinical studies have shown that the anti-TNF-alpha therapy improves cognition function of AD patients rapidly. However, the underlying mechanism remains elusive. The present study investigates the effects of intracerebroventricular injection of the monoclonal TNF-alpha antibody, Infliximab, on the pathological features of AD in the APP/PS1 double transgenic mice. We found that Infliximab administration reduced the levels of TNF-alpha, amyloid plaques and tau phosphorylation as early as three days after daily injection of 150micrograms of Infliximab for three days. The number of CD11c-positive dendritic-like cells and the expression of CD11c were found to be increased concurrently after Infliximab injection. These data suggested that the CD11c-positive dendritic-like cells might contribute to the Infliximab-induced reduction of AD-like pathology. Further, our results support the use of anti-TNF-alpha for the treatment of AD.
Copyright © 2010. Published by Elsevier B.V.
PMID: 20971085

Therapeutic evaluation of etanercept in a model of traumatic brain injury. Chio CC, Lin JW, Chang MW, Wang CC, Kuo JR, Yang CZ, Chang CP. J Neurochem. 2010 Nov;115(4):921-9. doi: 10.1111/j.1471-4159.2010.06969.x. Epub 2010 Sep 28.


J. Neurochem. (2010) 115, 921-929. ABSTRACT: Antagonism of tumor necrosis factor-alpha with etanercept has proved to be effective in the treatment of spinal cord injury and centrally endotoxin-induced brain injury. However, etanercept may offer promise as therapy for traumatic brain injury (TBI). In this study, anesthetized rats, immediately after the onset of TBI, were divided into two major groups and given the vehicle solution (1mL/kg of body weight) or etanercept (5mg/kg of body weight) intraperitoneally once per 12h for consecutive 3?days. Etanercept caused attenuation of TBI-induced cerebral ischemia (e.g., increased cellular levels of glutamate and lactate-to-pyruvate ratio), damage (e.g., increased cellular levels of glycerol) and contusion and motor and cognitive function deficits. TBI-induced neuronal apoptosis (e.g., increased numbers of terminal deoxynucleotidyl transferase ?UTP nick-end labeling and neuronal-specific nuclear protein double-positive cells), glial apoptosis (e.g., increased numbers of terminal deoxynucleotidyl transferase UTP nick-end labeling and glial fibrillary acidic protein double-positive cells), astrocytic (e.g., increased numbers of glial fibrillary acidic protein positive cells) and microglial (e.g., increased numbers of ionized calcium-binding adapter molecule 1-positive cells) activation and activated inflammation (e.g., increased levels of tumor necrosis factor-alpha, interleukin-1? and interleukin-6) were all significantly reduced by etanercept treatment. These findings suggest that etanercept may improve outcomes of TBI by penetrating into the cerebrospinal fluid in rats. © 2010 The Authors. Journal of Neurochemistry © 2010 International Society for Neurochemistry.

An association study of 21 potential Alzheimer’s disease risk genes in a Finnish population. Sarajärvi T, Helisalmi S, Antikainen L, Mäkinen P, Koivisto AM, Herukka SK, Haapasalo A, Soininen H, Hiltunen M. J Alzheimers Dis. 2010;21(3):763-7.


Alzheimer’s disease (AD) is a genetically complex disorder encompassing several individual susceptibility genes with low risk effects. To assess the risk gene effects in a cohort consisting of 1300 Finnish AD patients and controls, 21 candidate gene polymorphisms were selected for genotyping on the basis of the meta-analyses retrieved from the AlzGene database. A significant genotype and allele association with AD was observed with rs1800629 in the tumor necrosis factor-alpha (TNF). Risk analysis revealed a protective effect for the minor allele carriers of rs1800629. This suggests that genetic alteration in TNF gene may play a role in AD.

Higher Serum sTNFR1 Level Predicts Conversion from Mild Cognitive Impairment to Alzheimer’s Disease. Diniz BS, Teixeira AL, Ojopi EB, Talib LL, Mendonça VA, Gattaz WF, Forlenza OV. J Alzheimers Dis. 2010 Oct 7.


The activation of inflammatory cascades has been consistently demonstrated in the pathophysiology of Alzheimer’s disease (AD). Among several putative neuroinflammatory mechanisms, the tumor necrosis factor alpha (TNF-alpha) signaling system has a central role in this process. Recent evidence indicates that the abnormal production of inflammatory factors may accompany the progression from mild cognitive impairment (MCI) to dementia. We aimed to examine serum levels of TNFalpha and its soluble receptors (sTNFR1 and sTNFR2) in patients with MCI and AD as compared to cognitively unimpaired elderly subjects. We further aimed to investigate whether abnormal levels of these cytokines predict the progression from MCI to AD upon follow-up. We utilized cross-sectional determination of serum levels of TNF-alpha, sTNFR1, and sTNFR2 (ELISA method) in a test group comprising 167 older adults (31 AD, 72 MCI, and 64 healthy controls), and longitudinal reassessment of clinical status after 18.9 ± 10.0 months. At baseline, there were no statistically significant differences in serum TNF-alpha, sTNFR1, and sTNFR2 between patients with MCI and AD as compared to controls. Nevertheless, patients with MCI who progressed to AD had significantly higher serum sTNFR1 levels as opposed to patients who retained the diagnosis of MCI upon follow-up (p=0.03). Cox regression analysis showed that high serum sTNFR1 levels predicted the conversion from MCI to AD (p=0.003), whereas no significant differences were found with respect to serum levels of TNF-alpha and sTNFR2. Abnormal activation of TNF-alpha signaling system, represented by increased expression of sTNFR1, is associated with a higher risk of progression from MCI to AD.