Physiologic modulation of natural killer cell activity as an index of Alzheimer's disease progression



Paolo Prolo1,*, Francesco Chiappelli1, Alberto Angeli2, Andrea Dovio2,Paola Perotti2, Marisa Pautasso3, Maria Luisa Sartori2, Laura Saba2, Stefano Mussino2, Thomas Fraccalini4, Fausto Fantó4, Cristina Mocellini5, Maria Gabriella Rosso5, 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. Luigi Gonzaga, Orbassano, Italy; 5Neurology, A.S.O. S. Croce e Carle, Cuneo, Italy


Email; * Corresponding author


Article Type

Current Trends



received March 14, 2007; accepted March 20, 2006; published online March 21, 2007



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 10-6M.  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” (Δ > 2 points) or to a “slow progression” group (Δ < 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.



Alzheimer’s disease (AD); natural killer (NK) cells; NK cytotoxic activity; cortisol; interleukin (IL)-2; psychoimmunology



Prolo et al., Bioinformation 1(9): 363-366 (2007)


Edited by







Biomedical Informatics



This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.