Immunology Letters 117 (2008) 198–202 Contents lists available at ScienceDirect Immunology Letters j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / Differences of peripheral inflammatory markers between mild cognitive impairment and Alzheimer’s disease Paloma Bermejo a,∗ , Sagrario Mart´ ın-Arag ´ on a , Juana Bened´ ı a , Cristina Sus´ ın a , Emanuela Felici a , Pedro Gil b , Jos´ e Manuel Ribera b , ´ Angel M a Villar a a Departamento de Farmacolog ´ ıa, Facultad de Farmacia, Universidad Complutense de Madrid, Avenida de la Complutense s/n, 28040 Madrid, Spain b Servicio de Geriatr ´ ıa, Hospital Universitario Cl ´ ınico San Carlos, C/Profesor Mart ´ ın Lagos s/n, 28040 Madrid, Spain a r t i c l e i n f o Article history: Received 9 January 2008 Received in revised form 30 January 2008 Accepted 12 February 2008 Available online 7 March 2008 Keywords: Mild cognitive impairment Alzheimer’s disease Peripheral inflammatory markers IL-6 TNF-␣ IFN-␣ COX-2 a b s t r a c t Multiple pathogenic factors may contribute to the pathophysiology of Alzheimer’s disease (AD). Peripheral markers have been used to assess biochemical alterations associated with AD and mild cognitive impair- ment (MCI) involved in its pathophysiology. The present study was conducted to evaluate inflammatory peripheral markers in elderly patients with MCI, patients with AD and normal elderly subjects. We mea- sured plasma levels of different cytokines (IL-6, TNF-␣ and IFN-␣) and platelet levels of cyclooxigenase-2 (COX-2) from 34 patients with MCI, 45 patients with AD and 28 age-matched control subjects. MCI and AD patients showed similarities in TNF-␣ and COX-2 levels, and differences in IL-6 and INF-␣.Whereas augmented IL-6 levels have been found in AD patients, a significant increase in INF- ␣ has been detected only in patients with MCI possibly associated with the depression stage frequently found in cognitive impairment. In conclusion, inflammatory response may be an early factor in AD development and these changes in circulating markers are possibly related to the progression of MCI to AD. © 2008 Elsevier B.V. All rights reserved. 1. Introduction Alzheimer’s disease (AD) is a progressive neurodegenerative dis- order characterized by irreversible impairment of cognitive and memory functions and a physical deterioration.The aetiology of AD is complex and still largely unclear. Multiple pathogenic fac- tors may be involved in the pathology of AD. Several studies have shown the importance of oxidative stress in the pathogenesis of AD that means an imbalance between the formation and spread of reactive oxygen species and antioxidant defences [1]. A large body of evidence supports the hypothesis of a direct contribution of the inflammatory response to the neurodegeneration associated with AD. The main pathological features in the Alzheimer’s brain are progressive depositions of amyloid protein plaques between nerve cells and neurofibrillary tangles within the nerve cells [2]. Inflammatory mediators, including inflammatory cytokines, are highly expressed in the vicinity of ␤-amyloid (␤A) deposits and neurofibrillary tangles. A wide range of inflammatory markers, typ- ically absent in the normal elderly population, have been found in AD [3]. Cytokines such as interleukin-1␤ (IL-1 ␤), tumour necro- sis factor-␣ (TNF-␣), and interleukin-6 (IL-6), which have been ∗ Corresponding author. Tel.: +34 91 394 17 67; fax: +34 91 394 17 26. E-mail address: bescos@farm.ucm.es (P. Bermejo). clearly involved in the inflammatory process located close to amy- loid plaques, might be cytotoxic when chronically produced and might stimulate the production of ␤A peptides. Cytokines pre- sumably subserve similar intercellular and intracellular signalling processes in microglia and astrocytes as they do in the periphery [4]. An important role of local inflammation in AD has been sug- gested.High levels of TNF-␣ and IL-6 have been reported in the cerebrospinal fluid of patients with vascular dementia [5,6] sug- gesting a possible involvement of inflammatory mechanisms in the pathogenesis of cognitive impairment in patients with cerebrovas- cular disease. Furthermore, a number of studies have proven that brain inflammation was an important factor in neurodegenerative disorders [7,8]. AD has a multifactorial pathogenesis and its challenge is the early diagnosis. A large body of evidence shows that the risk of MCI patients for developing AD increases every year after the diag- nosis. MCI is characterized by isolated memory impairment that does not interfere with activities of daily living and is considered as a group at high risk to develop dementia over time[9]. Some experts believe that MCI patients have a 10 times greater risk of progressing to AD. Researchers are interested in understanding the relationship between MCI and the progression to the early stage of AD and whether or not MCI is an initial stage and a risk factor of AD [10,11]. 0165-2478/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.imlet.2008.02.002