Neutrophil Gelatinase-Associated Lipocalin and its Receptors in Alzheimer's Disease (AD) Brain Regions: Differential Findings in AD with and without Depression

Abstract

Co-existing depression worsens Alzheimer's disease (AD) pathology. Neutrophil gelatinase-associated lipocalin (NGAL) is a newly identified (neuro)inflammatory mediator in the pathophysiologies of both AD and depression. This study aimed to compare NGAL levels in healthy controls, AD without depression (AD-D), and AD with co-existing depression (ADD) patients. Protein levels of NGAL and its receptors, 24p3R and megalin, were assessed in nine brain regions from healthy controls (n = 19), AD-D (n = 19), and ADD (n = 21) patients. NGAL levels in AD-D patients were significantly increased in brain regions commonly associated with AD. In the hippocampus, NGAL levels were even further increased in ADD subjects. Unexpectedly, NGAL levels in the prefrontal cortex of ADD patients were comparable to those in controls. Megalin levels were increased in BA11 and amygdala of ADD patients, while no changes in 24p3R were detected. These findings indicate significant differences in neuroimmunological regulation between AD patients with and without co-existing depression. Considering its known effects, elevated NGAL levels might actively promote neuropathological processes in AD with and without depression.