Affiliations: [a] Laboratory of Neuroscience – LIM 27, Department and Institute of Psychiatry, Faculty of Medicine, University of Sao Paulo, Brazil | [b] Group of Neuroimmunology, Laboratory of Immunopharmacology, Institute of Biological Sciences and School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil
Correspondence:
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Correspondence to: Breno Satler Diniz, MD, Laboratory of Neuroscience, Institute of Psychiatry, Rua Dr. Ovidio Pires de Campos 785, 3th floor, 05403-010, São Paulo – SP, Brazil. Tel.: +55 11 3069 7267; Fax +55 11 3069 8010; E-mail: brenosatler@usp.br.
Note: [1] Authors contributed equally to this work.
Abstract: 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 α (TNF-α) 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 TNF-α 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-α, 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-α, 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-α and sTNFR2. Abnormal activation of TNF-α signaling system, represented by increased expression of sTNFR1, is associated with a higher risk of progression from MCI to AD.
