Locus coeruleus integrity correlates with plasma soluble Axl levels in Alzheimer's disease patients

INTRODUCTION: Locus coeruleus (LC) is one of the earliest structures altered in Alzheimer's disease (AD). Inflammation is also now considered critical in AD pathology, early stage included. However, no association between LC degeneration and the peripheral inflammation has been reported yet. METHODS: A cohort of 102 patients was studied for which both magnetic resonance imaging (MRI) scans and blood samples were available. LC integrity was assessed by MRI, and plasma soluble TAMs (Tyro3, Axl, and MerTK) receptor levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: We found that plasma levels of the soluble TAMs receptor Axl were correlated with LC rostral degeneration in the whole cohort (p = 0.007), as well as in the AD+ group (p = 0.017), but not in the AD– group. DISCUSSION: These results uncover a new relationship between peripheric markers of inflammation and central early AD neurodegeneration. Highlights: In Alzheimer's disease, no link between locus coeruleus degeneration and microglial activation was reported. Plasma Axl, Tyro3, and MerTK levels and locus coeruleus integrity were assessed in Alzheimer's disease patients. Locus coeruleus integrity positively correlates with plasma AXL, linked to microglia activation. Axl–noradrenergic signaling interplay deserves further larger longitudinal studies.