Amyloid beta and tau are associated with the dual effect of neuroinflammation on neurodegeneration

IF 11.1 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-09-29 DOI:10.1002/alz.70746

Guilherme Povala, Bruna Bellaver, Marco Antônio De Bastiani, João Pedro Ferrari-Souza, Cristiano S. Aguzzoli, Douglas T. Leffa, Pamela C. L. Ferreira, Firoza Z. Lussier, Andreia Rocha, Hussein Zalzale, Carolina Soares, Guilherme Bauer-Negrini, Joseph Therriault, Nesrine Rahmouni, Jenna Stevenson, Stijn Servaes, Cécile Tissot, Bruno Zatt, Thomas K. Karikari, Milos D. Ikonomovic, Victor L. Villemagne, Serge Gauthier, Eduardo R. Zimmer, Dana L. Tudorascu, Andrea L. Benedet, Pedro Rosa-Neto, Tharick A. Pascoal

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引用次数: 0

Abstract

INTRODUCTION

Current literature presents conflicting results regarding the impact of neuroinflammation on Alzheimer's disease (AD)-related neurodegeneration. While some studies suggest that neuroinflammation potentiates neurodegeneration, others indicate a protective effect.

METHODS

We evaluated 145 individuals with positron emission tomography (PET) for amyloid beta (Aβ), tau, and translocator protein (TSPO), a proxy of neuroinflammation, to test the hypothesis that Aβ and tau are associated with the dual effect of neuroinflammation on neurodegeneration across the AD continuum.

RESULTS

The detrimental effects of neuroinflammation on gray matter density occurred in two waves. The first neuroinflammation-related detrimental wave was associated with brain Aβ deposition, while the second was with widespread tau tangle pathology. Furthermore, the concomitant presence of neuroinflammation, Aβ, and tau was associated with faster cognitive decline over 2 years.

CONCLUSIONS

Our results support a model in which Aβ- and tau-associated neuroinflammation are related to two waves of deleterious effects on AD-related neurodegeneration.

Highlights

Two waves of detrimental neuroinflammation effects on brain density associated with Aβ or tau.
Aβ associated with deleterious effect of neuroinflammation on brain density in early AD.
Tau associated with deleterious effect of neuroinflammation on brain density in late AD.
Interactions of Aβ, tau, and neuroinflammation are associated with cognitive decline.

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淀粉样蛋白β和tau蛋白与神经炎症对神经变性的双重作用有关。

关于神经炎症对阿尔茨海默病（AD）相关神经变性的影响，目前的文献给出了相互矛盾的结果。虽然一些研究表明神经炎症会增强神经退行性变，但其他研究表明神经炎症有保护作用。方法：我们用正电子发射断层扫描（PET）对145名患者进行了淀粉样蛋白β (a β)、tau和转运蛋白（TSPO）的评估，以验证a β和tau与AD连续体中神经炎症对神经退行性变的双重作用有关的假设。结果神经炎症对脑灰质密度的影响分两波发生。第一种与神经炎症相关的有害波与脑Aβ沉积有关，而第二种与广泛的tau缠结病理有关。此外，神经炎症、Aβ和tau的同时存在与2年内认知能力下降更快有关。结论我们的研究结果支持a β-和tau相关的神经炎症与ad相关神经退行性变的两波有害影响相关的模型。两波有害的神经炎症对与Aβ或tau相关的脑密度的影响。Aβ与早期AD患者神经炎症对脑密度的有害影响有关。Tau蛋白与阿尔茨海默病晚期神经炎症对脑密度的有害影响有关。Aβ、tau蛋白和神经炎症的相互作用与认知能力下降有关。

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.