Abstract
Patients with Alzheimer's disease (AD) are characterized by an altered sensitivity to cortisol-mediated modulation of circulating lymphocytes. Longitudinal studies are needed to address the clinical applicability of these abnormalities as prognostic factors. Therefore, we designed a longitudinal study to address the clinical applicability of physiologic modulation of Natural Killer (NK) cell activity as a prognostic factor in AD. NK activity was assessed as baseline measurement and in response to modulation by cortisol at 10(-6)M. To verify the immunophysiological integrity of the NK cell population, we tested augmentation of NK cytotoxicity by human recombinant interleukin (IL)-2 (100 IU/ml) as control. The response to modulation by cortisol or by IL-2 was significantly greater in patients with AD. Based on change in the Mini-Mental State score at entry and at 18 months, patients with AD could be assigned to a "fast progression" (Delta > 2 points) or to a "slow progression" group (Delta <or= 2 points). The change in the response of NK cytotoxic activity to cortisol, and the strength of the association of this parameter with circulating activated T cells in time was greater in patients with Fast Progression vs. Slow Progression AD. These results suggest that changes in the response of NK cells to negative (e.g., cortisol) or positive modifiers (e.g., IL-2) follow progression of AD.
Highlights
Alzheimer's disease (AD) is a progressive disease of the brain caused by the deposit of β Amyloid protein
Current interventions for AD include acetylcholinesterase inhibitors (e.g., Donezepil, [Aricept®]) that are indicated for patients with early symptoms of disease. [1, 2, 3] Recent data indicate a significant involvement of the T cell-mediated [4, 5], as well as the inflammatory arm [5, 6, 7] of the immune system, which appears to be correlated to the severity of AD. [5, 8] Both in vivo and in vitro studies have demonstrated individual differences, which can be attributed to variables specific to each individual patient
Dysregulations in Natural Killer (NK) responses are modulated by adaptive physiological processes, i.e., allostasis [5] that may be intrinsic to immune regulation (e.g., IL-2), or that may involve nonimmune factors, such as products of the neuroendocrine system. [9]
Summary
Physiologic modulation of natural killer cell activity as an index of Alzheimer's disease progression. Paolo Prolo1*, Francesco Chiappelli, Alberto Angeli, Andrea Dovio, Paola Perotti, Marisa Pautasso, Maria Luisa Sartori, Laura Saba, Stefano Mussino, Thomas Fraccalini, Fausto Fantó, Cristina Mocellini, Maria Gabriella Rosso and Enzo Grasso5 1Division of Oral Biology & Medicine, UCLA School of Dentistry, Los Angeles, CA 90095-1668, West-Los Angeles, Veterans. Administration Medical Center, Los Angeles, CA 90025; 2Internal Medicine, University of Turin, A.S.O. S. Luigi Gonzaga, Orbassano, Italy; 3Flow Cytometry Lab, University of Turin, A.S.O. S. Luigi Gonzaga, Orbassano, Italy; 4Geriatrics, University of Turin, A.S.O. S
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
