阿尔茨海默病连续体中的瘦素和炎症途径：对神经胶质激活和神经精神症状的影响

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health Pub Date : 2025-05-26 DOI:10.1016/j.bbih.2025.101018

Fumihiko Yasuno , Kazuyuki Nakagome , Yoshie Omachi , Yasuyuki Kimura , Aya Ogata , Hiroshi Ikenuma , Junichiro Abe , Hiroyuki Minami , Takashi Nihashi , Kastunori Yokoi , Saori Hattori , Nobuyoshi Shimoda , Kensaku Kasuga , Takeshi Ikeuchi , Akinori Takeda , Takashi Sakurai , Kengo Ito , Takashi Kato

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引用次数: 0

摘要

由脂肪因子释放引发的慢性外周炎症可能扩展到大脑，潜在地影响阿尔茨海默病（AD）和神经精神症状（NPS）的病理进展。然而，目前尚不清楚瘦素是否以及如何导致脂肪组织功能障碍和痴呆之间的联系。本研究旨在探讨瘦素在脂肪源性炎症信号和认知障碍/NPS之间的作用。方法采用路径分析，探讨瘦素在AD病理患者（n = 15）中通过炎症途径与脂肪相关代谢功能障碍和痴呆之间的关系。变量包括血浆瘦素浓度、作为肥胖标志的体重指数（BMI），以及使用带有示踪剂11C-DPA-713 (11C-DPA-713结合电位[11C-DPA-713- bpnd]的转运蛋白(TSPO)-PET成像在体内评估局部神经炎症。认知功能采用阿尔茨海默病评估量表-日本认知量表（adas - jcog）进行测量，而NPS采用神经精神量表（NPI-Q）进行评估。结果回归分析结果显示，血浆瘦素浓度升高与BMI呈正相关，且可显著预测脑岛11C-DPA-713-BPND。此外，NPI-Q评分与脑岛11C-DPA-713-BPND相关。通径分析支持瘦素通过岛岛炎症将肥胖与NPS联系起来的作用。假设模型在原假设下与数据拟合良好[χ2 (3) = 0.63, p = 0.89]。这些发现强调了探索瘦素和脂肪组织功能障碍如何与神经炎症过程相互作用在AD患者中促进NPS的相关性。针对这些相互作用的干预措施可能是管理NPS的有希望的途径。

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Leptin and inflammatory pathways in the Alzheimer's disease continuum: Implications for glial activation and neuropsychiatric symptoms

Introduction

Chronic peripheral inflammation triggered by adipokine release may extend to the brain, potentially influencing the pathological progression of Alzheimer's disease (AD) and neuropsychiatric symptoms (NPS). However, it remains unclear whether and how leptin contributes to the link between adipose tissue dysfunction and dementia. This study aims to investigate the role of leptin in the connection between adipose-derived inflammatory signaling and cognitive impairment/NPS.

Methods

Path analysis was employed to explore how leptin relates to the association between adipose-related metabolic dysfunction and dementia through inflammatory pathways in patients with AD pathology (n = 15). Variables included plasma leptin concentration, body mass index (BMI) as a marker of adiposity, and in vivo assessments of regional neuroinflammation using translocator protein (TSPO)-PET imaging with the tracer ¹¹C-DPA-713 (¹¹C-DPA-713-binding potential [¹¹C-DPA-713-BP_ND]). Cognitive function was measured using the Alzheimer's Disease Assessment Scale-Japanese Cognitive Subscale (ADAS-J cog), while NPS were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q).

Results

Regression analysis demonstrated that higher plasma leptin concentrations positively correlated with BMI and significantly predicted ¹¹C-DPA-713-BP_ND in the insula. Additionally, NPI-Q scores were associated with ¹¹C-DPA-713-BP_ND in the insula. Path analysis supported leptin's role linking adiposity to NPS through insular inflammation. The hypothesized model fit the data well under the null hypothesis [χ² (3) = 0.63, p = 0.89].

Discussion

These findings underscore the relevance of exploring how leptin and adipose tissue dysfunction interact with neuroinflammatory processes in contributing to NPS in the patients in the AD continuum. Interventions targeting these interactions could represent promising avenues for managing NPS.

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来源期刊

Brain, behavior, & immunity - health Biological Psychiatry, Behavioral Neuroscience

CiteScore

8.50

自引率

0.00%

发文量

审稿时长

97 days