Abstract
BackgroundStudies suggest a role of the innate immune system, including the activity of neutrophils, in neurodegeneration related to Alzheimer’s disease (AD), but prospective cognitive data remain lacking in humans. We aimed to investigate the predictive relationship between neutrophil-associated inflammatory proteins in peripheral blood and changes in memory and executive function over 1 year in patients with AD.MethodsParticipants with AD were identified from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Neutrophil gelatinase-associated lipocalin (NGAL), myeloperoxidase (MPO), interleukin-8 (IL-8), macrophage inflammatory protein-1 beta (MIP-1β), and tumor necrosis factor (TNF) were assayed by luminex immunofluorescence multiplex assay at baseline. Confirmatory factor analysis was used to test an underlying neutrophil associated plasma inflammatory factor. Composite z-scores for memory and executive function were generated from multiple tests at baseline and at 1 year. A multiple linear regression model was used to investigate the association of the baseline inflammatory factor with changes in memory and executive function over 1 year.ResultsAmong AD patients (n = 109, age = 74.8 ± 8.1, 42% women, Mini Mental State Examination [MMSE] = 23.6 ± 1.9), the neutrophil-related inflammatory proteins NGAL (λ = 0.595, p < .001), MPO (λ = 0.575, p < .001), IL-8 (λ = 0.525, p < .001), MIP-1β (λ = 0.411, p = .008), and TNF (λ = 0.475, p < .001) were found to inform an underlying factor. Over 1 year, this inflammatory factor predicted a decline in executive function (β = − 0.152, p = 0.015) but not memory (β = 0.030, p = 0.577) in models controlling for demographics, brain atrophy, white matter hyperintensities, the ApoE ε4 allele, concomitant medications, and baseline cognitive performance.ConclusionsAn inflammatory factor constructed from five neutrophil-related markers in peripheral blood predicted a decline in executive function over 1 year in people with mild AD.
Highlights
Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by the deposition of amyloidβ plaques and neurofibrillary tangles in the brain [1]
An inflammatory factor constructed from five neutrophil-related markers in peripheral blood predicted a decline in executive function over 1 year in people with mild AD
The present study examines five neutrophil-related plasma markers in peripheral blood: myeloperoxidase (MPO) which is responsible for neutrophil-related oxidative stress [4, 18], neutrophil gelatinase-associated lipocalin (NGAL) a neutrophil secreted anti-microbial molecule [4, 19], tumor necrosis factor (TNF) which is involved in neutrophil activation and survival [20, 21], and interleukin-8 (IL-8) and macrophage inflammatory protein-1β (MIP-1β), which both play a role in neutrophil trafficking and activation and which are both secreted by activated neutrophils [22]
Summary
Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by the deposition of amyloidβ plaques and neurofibrillary tangles in the brain [1]. It is the most prevalent form of dementia seen in people over 65 years of age, and it causes severe deficits in memory and executive function. It is well established that patients with AD have elevated immune activation, which can be indicated by inflammatory markers in peripheral blood; studies have shown inconsistent results [2, 3]. Studies suggest a role of the innate immune system, including the activity of neutrophils, in neurodegeneration related to Alzheimer’s disease (AD), but prospective cognitive data remain lacking in humans. We aimed to investigate the predictive relationship between neutrophil-associated inflammatory proteins in peripheral blood and changes in memory and executive function over 1 year in patients with AD
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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 call
