Luuk E. de Vries, Inge Huitinga, Helmut W. Kessels, Dick F. Swaab, Joost Verhaagen
{"title":"The concept of resilience to Alzheimer’s Disease: current definitions and cellular and molecular mechanisms","authors":"Luuk E. de Vries, Inge Huitinga, Helmut W. Kessels, Dick F. Swaab, Joost Verhaagen","doi":"10.1186/s13024-024-00719-7","DOIUrl":null,"url":null,"abstract":"Some individuals are able to maintain their cognitive abilities despite the presence of significant Alzheimer’s Disease (AD) neuropathological changes. This discrepancy between cognition and pathology has been labeled as resilience and has evolved into a widely debated concept. External factors such as cognitive stimulation are associated with resilience to AD, but the exact cellular and molecular underpinnings are not completely understood. In this review, we discuss the current definitions used in the field, highlight the translational approaches used to investigate resilience to AD and summarize the underlying cellular and molecular substrates of resilience that have been derived from human and animal studies, which have received more and more attention in the last few years. From these studies the picture emerges that resilient individuals are different from AD patients in terms of specific pathological species and their cellular reaction to AD pathology, which possibly helps to maintain cognition up to a certain tipping point. Studying these rare resilient individuals can be of great importance as it could pave the way to novel therapeutic avenues for AD.","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":"32 1","pages":""},"PeriodicalIF":14.9000,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Neurodegeneration","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13024-024-00719-7","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Some individuals are able to maintain their cognitive abilities despite the presence of significant Alzheimer’s Disease (AD) neuropathological changes. This discrepancy between cognition and pathology has been labeled as resilience and has evolved into a widely debated concept. External factors such as cognitive stimulation are associated with resilience to AD, but the exact cellular and molecular underpinnings are not completely understood. In this review, we discuss the current definitions used in the field, highlight the translational approaches used to investigate resilience to AD and summarize the underlying cellular and molecular substrates of resilience that have been derived from human and animal studies, which have received more and more attention in the last few years. From these studies the picture emerges that resilient individuals are different from AD patients in terms of specific pathological species and their cellular reaction to AD pathology, which possibly helps to maintain cognition up to a certain tipping point. Studying these rare resilient individuals can be of great importance as it could pave the way to novel therapeutic avenues for AD.
尽管阿尔茨海默病(AD)的神经病理变化显著,但有些人仍能保持认知能力。这种认知与病理之间的差异被称为恢复力,并已发展成为一个广受争议的概念。认知刺激等外部因素与对老年痴呆症的恢复力有关,但确切的细胞和分子基础尚未完全明了。在这篇综述中,我们将讨论该领域目前使用的定义,重点介绍用于研究抗逆转录病毒能力的转化方法,并总结从人类和动物研究中得出的抗逆转录病毒能力的细胞和分子基础,这些研究在过去几年中受到越来越多的关注。从这些研究中可以看出,具有恢复力的个体在特定病理类型及其对 AD 病理的细胞反应方面与 AD 患者不同,这可能有助于将认知能力维持到某个临界点。研究这些罕见的恢复能力强的个体具有重要意义,因为它可以为新的注意力缺失症治疗途径铺平道路。
期刊介绍:
Molecular Neurodegeneration, an open-access, peer-reviewed journal, comprehensively covers neurodegeneration research at the molecular and cellular levels.
Neurodegenerative diseases, such as Alzheimer's, Parkinson's, Huntington's, and prion diseases, fall under its purview. These disorders, often linked to advanced aging and characterized by varying degrees of dementia, pose a significant public health concern with the growing aging population. Recent strides in understanding the molecular and cellular mechanisms of these neurodegenerative disorders offer valuable insights into their pathogenesis.