title: Physiologic modulation of natural killer cell activity as an index of Alzheimer's disease progression.
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.
authors.affiliation: Division of Oral Biology & Medicine, UCLA School of Dentistry, Los Angeles, CA 90095-1668, USA. pprolo@dent.ucla.edu
authors.forename: Paolo
authors.initials: P
authors.lastname: Prolo
authors.forename: Francesco
authors.initials: F
authors.lastname: Chiappelli
authors.forename: Alberto
authors.initials: A
authors.lastname: Angeli
authors.forename: Andrea
authors.initials: A
authors.lastname: Dovio
authors.forename: Paola
authors.initials: P
authors.lastname: Perotti
authors.forename: Marisa
authors.initials: M
authors.lastname: Pautasso
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Sartori
authors.forename: Laura
authors.initials: L
authors.lastname: Saba
authors.forename: Stefano
authors.initials: S
authors.lastname: Mussino
authors.forename: Thomas
authors.initials: T
authors.lastname: Fraccalini
authors.forename: Fausto
authors.initials: F
authors.lastname: Fantó
authors.forename: Cristina
authors.initials: C
authors.lastname: Mocellini
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Rosso
authors.forename: Enzo
authors.initials: E
authors.lastname: Grasso