Alzheimer's disease; blood‐based biomarkers; locus coeruleus; neuroinflammation; noradrenaline; Receptor Protein-Tyrosine Kinases; Axl Receptor Tyrosine Kinase; Proto-Oncogene Proteins; AXL protein, human; Biomarkers; Humans; Male; Female; Aged; Magnetic Resonance Imaging; Biomarkers/blood; Cohort Studies; Middle Aged; Alzheimer Disease/blood; Alzheimer Disease/pathology; Alzheimer Disease/diagnostic imaging; Locus Coeruleus/pathology; Locus Coeruleus/diagnostic imaging; Receptor Protein-Tyrosine Kinases/blood; Proto-Oncogene Proteins/blood
Abstract :
[en] [en] 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.
Disciplines :
Neurology
Author, co-author :
Galgani, Alessandro ✱; Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy
Lombardo, Francesco; Department of Radiology, Fondazione Toscana "G. Monasterio", Pisa, Italy
Martini, Nicola ; Department of Radiology, Fondazione Toscana "G. Monasterio", Pisa, Italy
Scotto, Marco ; Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy ; Istituto Italiano di Tecnologia, Genoa, Italy
Tognoni, Gloria; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
Siciliano, Gabriele ; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
Ceravolo, Roberto ; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
Giorgi, Filippo S ✱; Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy ; I.R.C.C.S. Stella Maris, Calambrone, Pisa, Italy
HENEKA, Michael ✱; University of Luxembourg ; Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
✱ These authors have contributed equally to this work.
External co-authors :
yes
Language :
English
Title :
Locus coeruleus integrity correlates with plasma soluble Axl levels in Alzheimer's disease patients.
Publication date :
July 2025
Journal title :
Alzheimer's and Dementia: the Journal of the Alzheimer's Association
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