Massive changes in gene expression and their cause(s) can be a unifying principle in the pathobiology of Alzheimer's disease

IF 11.1 1区医学 Q1 CLINICAL NEUROLOGY Alzheimer's & Dementia Pub Date : 2025-02-06 DOI:10.1002/alz.14555

Paul D. Coleman, Elaine Delvaux, Jeffrey H. Kordower, Ashley Boehringer, Carol J. Huseby

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Abstract

Understanding of the biology of Alzheimer's disease (AD) has long been fragmented, with various investigators concentrating on amyloid beta (Aβ) or tau, inflammation, cell death pathways, misfolded proteins, glia, and more. Yet data from multiple authors has repeatedly shown altered expression of myriad genes related to these seemingly disparate phenomena. In 2022, Morgan et al. organized the massive data on changes in AD in a meticulous survey of the literature and related these changes to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Their data showed that 91% of the known KEGG pathways are involved in AD and that many of these pathways are represented by the known cellular/molecular phenomena of AD. Such data then raise the fundamental question: What mechanism(s) may be responsible for such widespread changes in gene expression? We review evidence for a unifying model based on sequestrations in stress granules and alteration of nucleocytoplasmic transport in AD.

Highlights

In Alzheimer's disease (AD), critical changes take place in neurons before the appearance of plaques or tangles.
Addressing these early changes provides a path to early detection and effective intervention in AD.

Abstract Image

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基因表达的巨大变化及其原因可能是阿尔茨海默病病理生物学的统一原则

长期以来，对阿尔茨海默病（AD）生物学的理解一直是碎片化的，不同的研究人员专注于β淀粉样蛋白（Aβ）或tau蛋白、炎症、细胞死亡途径、错误折叠的蛋白质、胶质细胞等。然而，多位作者的数据反复表明，与这些看似不同的现象有关的无数基因的表达发生了变化。2022年Morgan等人在细致的文献调查中整理了大量关于AD变化的数据，并将这些变化与京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes， KEGG）通路联系起来。他们的数据显示，91%的已知KEGG通路与AD有关，其中许多通路由AD的已知细胞/分子现象所代表。这样的数据提出了一个基本的问题：什么机制可能导致基因表达如此广泛的变化？我们回顾了基于应力颗粒的隔离和AD核胞质转运改变的统一模型的证据。在阿尔茨海默病（AD）中，在斑块或缠结出现之前，神经元发生了关键的变化。解决这些早期变化提供了早期发现和有效干预阿尔茨海默病的途径。

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.