Leukocytes and Endothelial Cells Participate in the Pathogenesis of Alzheimer's Disease: Identifying New Biomarkers Mirroring Metabolic Alterations.

ABSTRACT

Alzheimer's disease (AD) is a neurodegenerative disorder marked by amyloid-ß accumulation, tau dysfunction, and neuroinflammation, involving endothelial cells and leukocytes. The breakdown of the blood-brain barrier allows immune cell infiltration, intensifying inflammation. A decreased ratio of Connexin-37 (Cx37, also known as GJA4 Gap Junction Protein Alpha 4) and Prolyl Hydroxylase Domain-Containing Protein 3 (PHD3, also known as EGLN3 Egl-9 Family Hypoxia Inducible Factor 3), Cx37/PHD3, consistently observed in different AD-related models, may represent a novel potential biomarker of AD, albeit the exact mechanisms underlying this phenomenon, most likely based on gap junction-mediated cellular interaction that modulate the cellular metabolite status, remain to be fully elucidated.