Memory decline correlates with increased plasma cytokines in amyloid-beta (1-42) rat model of Alzheimer's disease.

Abstract

Dysregulation of inflammatory markers like cytokines is implicated in the pathophysiology of Alzheimer's disease (AD). Altered level of these cytokines show that pathogenesis of AD is beyond dysfunction of neurons resulting from amyloid beta accumulation but involves neuroinflammatory mechanisms elicited by the neuroimmune cell. In this study, we investigated the effect of amyloid-beta (1-42) (Aβ(1-42)) on memory and how inflammatory markers respond to this model of AD. Male Sprague-Dawley rats were used for this study. The animals were randomly divided into four groups euthanized on day 3, 7, 10 and 14 post-lesion with amyloid-beta (5μg/5μl) while corresponding control groups were stereotaxically injected with a vehicle (5μl of 0.01M phosphate- buffered saline). The Morris water maze (MWM) test to access learning and memory was conducted pre and post-lesion and blood was collected through cardiac puncture on day 3, 7, 10 and 14 post lesion. Multiplex immunoassay was performed to determine the plasma levels of IL-1β, IL-6, IL-10 and TNF-α. Our results showed impaired spatial memory and elevated plasma levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) with a concomitantly lowered level of the anti-inflammatory cytokine (IL-10) in the Aβ(1-42) lesioned rats when compared to the vehicle groups. This study showed a negative correlation between the decline in performance of the spatial memory task and plasma levels of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α and positive correlation with the anti-inflammatory cytokine IL-10. In conclusion, this study most importantly demonstrated an association between progressive decline in spatial memory and increased plasma cytokine level induced by the infusion of Aβ(1-42).