Leptin levels are associated with body mass index and Alzheimer's disease in Down syndrome

IF 13 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-07-09 DOI:10.1002/alz.70448

Lorena Sordo, Annie Du, Vinutha Sandadi, Farheen B. Dustagheer, Jesse Pascual, Phong Ngo, Christy L. Hom, Eric Doran, Elizabeth Head

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Abstract

INTRODUCTION

Higher body mass index (BMI) is linked to greater risk of Alzheimer's disease (AD) and elevated plasma leptin levels correlate with cognitive decline and AD. Since obesity is a frequent feature in individuals with Down syndrome (DS), we investigated the association between obesity, the leptin pathway, and AD neuropathology in people with DS.

METHODS

Plasma concentrations of leptin and AD biomarkers were measured in 40 individuals (aged controls, Down syndrome and Alzheimer's disease [DSAD], and AD participants). Frontal cortex leptin, leptin receptors (LepRs), and leptin-associated proteins were measured in 73 individuals with DS, DSAD, and AD, and compared to age-matched controls using immunohistochemistry.

RESULTS

Individuals with DSAD had the highest plasma leptin levels, as well as the highest leptin resistance index and brain leptin deficiency. Plasma leptin levels were significantly associated with staging of AD neuropathology.

DISCUSSION

Leptin has the potential to be an early indicator and therapeutic target for AD in people with and without DS.

Highlights

Plasma leptin levels are increased in Down syndrome and Alzheimer's disease (DSAD).
Leptin resistance and brain leptin deficiency are present in Down syndrome (DS) and DSAD.
Plasma leptin levels are positively associated with staging of Alzheimer's disease (AD) neuropathology.

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瘦素水平与体重指数和唐氏综合症中的阿尔茨海默病有关

较高的身体质量指数（BMI）与阿尔茨海默病（AD）的风险增加有关，血浆瘦素水平升高与认知能力下降和AD相关。由于肥胖是唐氏综合征（DS）患者的常见特征，我们研究了唐氏综合征患者肥胖、瘦素通路和AD神经病理之间的关系。方法测量40例老年对照、唐氏综合征和阿尔茨海默病（DSAD）和AD参与者的血浆瘦素和AD生物标志物浓度。对73例DS、DSAD和AD患者的额叶皮质瘦素、瘦素受体（lepr）和瘦素相关蛋白进行了测量，并与年龄匹配的对照组进行了免疫组织化学比较。结果DSAD患者血浆瘦素水平最高，瘦素抵抗指数和脑瘦素缺乏症最高。血浆瘦素水平与AD神经病理分期显著相关。瘦素有可能成为伴有或不伴有退行性椎体滑移的AD患者的早期指标和治疗靶点。血浆瘦素水平在唐氏综合症和阿尔茨海默病（DSAD）中升高。在唐氏综合征（DS）和DSAD中存在瘦素抵抗和脑瘦素缺乏。血浆瘦素水平与阿尔茨海默病（AD）神经病理学分期呈正相关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.