Role of the innate immune response in the progression of Alzheimer’s disease

Abstract

Abstract Alzheimer’s disease (AD) is a progressive irreversible neurological brain disorder. Inflammation and immune alterations have been linked to AD, suggesting that the peripheral immune system plays a role during the asymptomatic period of AD. NK cells and neutrophils (PMN) participate in innate immune surveillance against intracellular pathogens and malignancy but their role in AD remains controversial. We have investigated changes in peripheral NK cell and PMN phenotypes and functions in amnestic mild cognitive impairment (aMCI, n = 10), patients with mild AD (mAD, n = 11), and healthy elderly controls (n = 10). Patients selected according to NINCDS-ADRDA criteria were classified using neuropsychological assessment tests. Phenotype analysis revealed differences in expression of CD16 (increased in mAD), NKG2A (decreased in aMCI), and TLR2 and TLR9 (both decreased in mAD) for NK and CD14 (increased in MCI). Functional assays revealed that NK cell killing activity and degranulation (CD107 expression) were unchanged in the three groups. In contrast, expression of the CD95 receptor was increased in aMCI and mAD. Granzyme B expression and cytokine production (TNFα, IFNγ) were increased in aMCI but not in mAD. Similarly, PMN phagocytosis and free radical production were differentially modulated in MCI and mAD patients. Our data suggest that the number of alterations observed in peripheral NK cells and neutrophils in aMCI represent an activation state compared to mAD patients and that may reflect an active immune response against a still to be defined aggression.