Abstract

Background: Among the pathogenic processes in Alzheimer’s Disease (AD), systemic inflammation, autophagy and metabolic alterations have been described. The double-stranded RNA-dependent protein kinase (PKR) is an ubiquitous cellular kinase involved in these several pathogenic processes, and previous studies reported its involvement in AD. PKR can be activated by phosphorylation (P_T451-PKR) and cleaved in catalytic form (PKR-KD). We have previously described a correlation between PKR activation in peripheral blood mononuclear cells (PBMCs) and cognitive status in advanced AD. However, the link between PKR’s activation in PBMCs and cognitive decline in AD remains unknown.
Methods: Thirty-one patients with AD were included. Acute and chronic inflammations were considered as exclusion criteria. Cognitive status was assessed with Mini Mental State Examination (MMSE) and AD assessment scale (ADAScog) at baseline, 6, 12 and 24 months of follow-up. PKR expression and its activation were measured using western blot at baseline, 12 and 24 months.
Results: At baseline, MMSE mean score was 20.5 ± 2.6; Except for total PKR expression between baseline and M12, no longitudinal significant variation of PKR activation was found. Higher PKR-KD activation was correlated with faster cognitive decline at an individual level at M6 (r=0.33, p=0.0453), M12 (r=0.48, p=0.0033) and M24 (r=0.36, p=0.0407). Other PKR forms were correlated with cognitive decline at M12.
Conclusions: Our results suggest that PKR activation in PBMCSs can predict cognitive decline in AD at an early stage at an individual level.

Keywords: Alzheimer’s disease; Cognitive decline; Chronic inflammations; Cognitive disorders