在阿尔茨海默病患者中，蓝斑核完整性与血浆可溶性Axl水平相关。
Locus coeruleus integrity correlates with plasma soluble Axl levels in Alzheimer's disease patients.
作者信息
Galgani Alessandro, Mary Arnaud, Lombardo Francesco, Martini Nicola, Scotto Marco, Tognoni Gloria, Siciliano Gabriele, Ceravolo Roberto, Giorgi Filippo S, Heneka Michael T
机构信息
Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy.
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, Luxembourg.
出版信息
Alzheimers Dement. 2025 Jul;21(7):e70434. doi: 10.1002/alz.70434.
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.
引言
蓝斑（LC）是阿尔茨海默病（AD）中最早发生改变的结构之一。炎症现在也被认为在AD病理中至关重要，包括早期阶段。然而，尚未有关于LC变性与外周炎症之间关联的报道。
方法
对102名患者进行了队列研究，这些患者均有磁共振成像（MRI）扫描结果和血液样本。通过MRI评估LC的完整性，并通过酶联免疫吸附测定（ELISA）测量血浆可溶性TAM（Tyro3、Axl和MerTK）受体水平。
结果
我们发现，在整个队列（p = 0.007）以及AD+组（p = 0.017）中，可溶性TAM受体Axl的血浆水平与LC Rostral变性相关，但在AD-组中无相关性。
讨论
这些结果揭示了炎症外周标志物与中枢早期AD神经变性之间的新关系。
要点
在阿尔茨海默病中，未报道蓝斑变性与小胶质细胞激活之间的联系。评估了阿尔茨海默病患者的血浆Axl、Tyro3和MerTK水平以及蓝斑完整性。蓝斑完整性与血浆AXL呈正相关，与小胶质细胞激活有关。Axl-去甲肾上腺素能信号相互作用值得进一步开展更大规模的纵向研究。
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