Transfixed by transgenics: how pathology assumptions are slowing progress in Alzheimer's disease and related dementia research

Abstract Model organisms of human diseases are invaluable tools for unraveling pathogenic mechanisms, identifying potential targets for drug development, and evaluating the therapeutic efficacy of candidates in preclinical trials. The utility of model organisms hinges upon their ability to faithfull...

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Main Author: Luciano D'Adamio
Format: Article
Language:English
Published: Springer Nature 2023-09-01
Series:EMBO Molecular Medicine
Online Access:https://doi.org/10.15252/emmm.202318479
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author Luciano D'Adamio
author_facet Luciano D'Adamio
author_sort Luciano D'Adamio
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description Abstract Model organisms of human diseases are invaluable tools for unraveling pathogenic mechanisms, identifying potential targets for drug development, and evaluating the therapeutic efficacy of candidates in preclinical trials. The utility of model organisms hinges upon their ability to faithfully replicate the underlying pathogenic mechanisms of the human disease. For rodent models of Alzheimer's disease (AD) and AD‐related dementias (ADRD), the limited translatability to human disease raises concerns about their overall utility. What factors contribute to this limitation? Is AD inherently too complex to be accurately modeled in nonhumans? Is the divergence between rodent brains and the human brain so pronounced that rodents are unsuitable as model organisms for AD? Or is it plausible that the commonly used rodent models don't capture the genuine pathogenic mechanisms underlying these diseases? This editorial discusses the challenges associated with transgenic models of AD and ADRD and offers some alternative approaches.
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spelling doaj-art-e28ff2500d7b44fa898dbf50a3a72a912025-08-20T03:46:19ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842023-09-0115111510.15252/emmm.202318479Transfixed by transgenics: how pathology assumptions are slowing progress in Alzheimer's disease and related dementia researchLuciano D'Adamio0Department of Pharmacology, Physiology & Neuroscience New Jersey Medical School, Brain Health Institute, Jacqueline Krieger Klein Center in Alzheimer's Disease and Neurodegeneration Research, Rutgers, The State University of New JerseyAbstract Model organisms of human diseases are invaluable tools for unraveling pathogenic mechanisms, identifying potential targets for drug development, and evaluating the therapeutic efficacy of candidates in preclinical trials. The utility of model organisms hinges upon their ability to faithfully replicate the underlying pathogenic mechanisms of the human disease. For rodent models of Alzheimer's disease (AD) and AD‐related dementias (ADRD), the limited translatability to human disease raises concerns about their overall utility. What factors contribute to this limitation? Is AD inherently too complex to be accurately modeled in nonhumans? Is the divergence between rodent brains and the human brain so pronounced that rodents are unsuitable as model organisms for AD? Or is it plausible that the commonly used rodent models don't capture the genuine pathogenic mechanisms underlying these diseases? This editorial discusses the challenges associated with transgenic models of AD and ADRD and offers some alternative approaches.https://doi.org/10.15252/emmm.202318479
spellingShingle Luciano D'Adamio
Transfixed by transgenics: how pathology assumptions are slowing progress in Alzheimer's disease and related dementia research
EMBO Molecular Medicine
title Transfixed by transgenics: how pathology assumptions are slowing progress in Alzheimer's disease and related dementia research
title_full Transfixed by transgenics: how pathology assumptions are slowing progress in Alzheimer's disease and related dementia research
title_fullStr Transfixed by transgenics: how pathology assumptions are slowing progress in Alzheimer's disease and related dementia research
title_full_unstemmed Transfixed by transgenics: how pathology assumptions are slowing progress in Alzheimer's disease and related dementia research
title_short Transfixed by transgenics: how pathology assumptions are slowing progress in Alzheimer's disease and related dementia research
title_sort transfixed by transgenics how pathology assumptions are slowing progress in alzheimer s disease and related dementia research
url https://doi.org/10.15252/emmm.202318479
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