Acosta-Martínez Maricedes, Carter Vanessa, Nessim Aviram, Panchal Radha, John Dora, Dhawan Jasbeer, Beach Thomas G, Serrano Geidy E, Sundermann Erin E, Biegon Anat
Department of Physiology & Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York, USA.
Department of Radiology, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York, USA.
Alzheimers Dement. 2025 Apr;21(4):e14603. doi: 10.1002/alz.14603.
Despite known sex differences in immune function and Alzheimer's disease (AD), most studies of neuroinflammation in AD have not been analyzed by sex.
We performed quantitative in vitro autoradiography of hippocampus, entorhinal cortex, and parietal cortex using [H]-PK1195 and [F]-T807. Proinflammatory microRNA (miRNA) expression in parietal cortex was measured by quantitative polymerase chain reaction (qPCR).
We found significant, region-dependent elevations of translocator protein (TSPO) density in AD relative to cognitively normal (CN) and mild cognitive impairment (MCI) in women but not men. Density of tau was increased in AD relative to CN and MCI in both sexes, but only women showed a significant positive correlation between tau and TSPO density. The expression of proinflammatory miRNAs was also significantly increased in AD versus CN or MCI women but not men.
Women are more susceptible than men to AD/tau-related neuroinflammation, supporting a sex-specific re-examination of the effects of neuroinflammation-targeting interventions in AD.
We show that neuroinflammation in Alzheimer's disease (AD) is modulated by sex in a region-specific manner. Neuroinflammation was highest in the subiculum and significant only in women. Inflammatory microRNAs (miRNAs) increased in the parietal cortex of women, but not men, with AD. Deposition of tau was highest in the entorhinal cortex and significant in both sexes. Density of tau and TSPO was positively and significantly correlated only in AD women.
尽管已知免疫功能和阿尔茨海默病（AD）存在性别差异，但大多数关于AD神经炎症的研究尚未按性别进行分析。
我们使用[H]-PK1195和[F]-T807对海马体、内嗅皮质和顶叶皮质进行了定量体外放射自显影。通过定量聚合酶链反应（qPCR）测量顶叶皮质中促炎微RNA（miRNA）的表达。
我们发现，与认知正常（CN）和轻度认知障碍（MCI）相比，AD患者中女性的转位蛋白（TSPO）密度在区域上有显著升高，而男性则没有。与CN和MCI相比，AD患者中tau的密度在两性中均增加，但只有女性的tau与TSPO密度之间存在显著正相关。与CN或MCI女性相比，AD女性中促炎miRNA的表达也显著增加，而男性则没有。
女性比男性更容易受到AD/ tau相关神经炎症的影响，这支持了对AD中针对神经炎症的干预措施的效果进行针对性别的重新审视。
我们表明，阿尔茨海默病（AD）中的神经炎症以区域特异性方式受到性别的调节。神经炎症在海马下托中最高，且仅在女性中显著。患有AD的女性顶叶皮质中的炎性微RNA（miRNA）增加，而男性则没有。tau的沉积在内嗅皮质中最高，且在两性中均显著。tau和TSPO的密度仅在AD女性中呈显著正相关。
