Microglial responses partially mediate the effect of Aβ on cognition in Alzheimer's disease

IF 13 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2024-10-11 DOI:10.1002/alz.14298

Lasse S. Madsen, Rola Ismail, Peter Parbo, Pernille L. Kjeldsen, Jeppe L. Schaldemose, Kim V. Hansen, Hanne Gottrup, Joel Aanerud, Simon F. Eskildsen, David J. Brooks

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Abstract

INTRODUCTION

Microglial responses are an integral part of Alzheimer's disease (AD) pathology and are associated with amyloid beta (Aβ) deposition. This study aimed to investigate the effects of Aβ and microglial responses on global cognitive impairment.

METHODS

In this longitudinal study, 28 patients with mild cognitive impairment and 11 healthy controls underwent ¹¹C-PK11195 and ¹¹C-Pittsburgh compound B positron emission tomography (PET), structural magnetic resonance imaging scans, and global cognitive ratings at baseline and 2-year follow-up. Correlations between PET uptake and global cognition were assessed. Additionally, the mediation effect of the microglial response on the association between Aβ load and global cognition was assessed.

RESULTS

Aβ load and the microglial response were both independently detrimental to global cognitive performance at baseline; however, at 2-year follow-up the association between Aβ load and global cognitive ratings was partially mediated by the microglial response.

DISCUSSION

As AD progresses, the associated microglial response partially mediates the detrimental effect of aggregated Aβ on cognition.

Highlights

This was a longitudinal study of amyloid beta (Aβ), microglial responses, and global cognitive performance.
Aβ and microglial responses both affect cognition in early Alzheimer's disease.
Microglial response partially mediates the effect of Aβ on cognition in later stages.

Abstract Image

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微胶质细胞反应部分介导了 Aβ 对阿尔茨海默病认知能力的影响。

简介小胶质细胞反应是阿尔茨海默病（AD）病理的一个组成部分，与淀粉样蛋白β（Aβ）沉积有关。本研究旨在探讨 Aβ 和小胶质细胞反应对整体认知障碍的影响：在这项纵向研究中，28 名轻度认知障碍患者和 11 名健康对照者接受了 11C-PK11195 和 11C 匹兹堡化合物 B 正电子发射断层扫描（PET）、结构性磁共振成像扫描，并在基线和 2 年随访时进行了总体认知评级。评估了 PET 摄取与总体认知之间的相关性。此外，还评估了小胶质细胞反应对 Aβ 负荷与整体认知之间关联的中介效应：结果：在基线时，Aβ负荷和微神经胶质细胞反应都对总体认知表现有独立的不利影响；然而，在2年的随访中，Aβ负荷和总体认知评分之间的关联部分由微神经胶质细胞反应所调节：讨论：随着 AD 的进展，相关的小胶质细胞反应部分介导了聚集的 Aβ 对认知的有害影响：这是一项关于淀粉样蛋白β（Aβ）、小胶质细胞反应和整体认知能力的纵向研究。淀粉样蛋白β和小胶质细胞反应都会影响早期阿尔茨海默氏症患者的认知能力。小胶质细胞反应部分介导了 Aβ 对后期认知能力的影响。

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.