Novel mouse model of Alzheimer's disease exhibits pathology through synergistic interactions among amyloid-β,tau,and reactive astrogliosis  

作　　者：Young-Eun Han Sunhwa Lim Seung Eun Lee Min-Ho Nam Soo-Jin Oh 

机构地区：[1]Brain Science Institute,Korea Institute of Science and Technology(KIST),Seoul 02792,Republic of Korea [2]Research Animal Resources Center,Korea Institute of Science and Technology(KIST),Seoul 02792,Republic of Korea

出　　处：《Zoological Research》2025年第1期41-53,共13页动物学研究(英文)

基　　金：supported by the National Research Foundation of Korea (NRF)funded by the Ministry of Science,ICT&Future Planning (2022R1A2C2006229,2022R1A6A3A01086868);Korea Dementia Research Project through the Korea Dementia Research Center (KDRC)funded by the Ministry of Health&Welfare and Ministry of Science and ICT,Republic of Korea (RS-2024-00345328);KIST Institutional Grant (2E32851)。

摘　　要：Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis.Developing effective diagnostic,preventative,and therapeutic strategies for AD necessitates the establishment of animal models that accurately recapitulate the pathophysiological processes of the disease.Existing transgenic mouse models have significantly contributed to understanding AD pathology but often fail to replicate the complexity of human AD.Additionally,these models are limited in their ability to elucidate the interplay among amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis due to the absence of spatially and temporally specific genetic manipulation.In this study,we introduce a novel AD mouse model(APP/PS1-TauP301L-Adeno mice)designed to rapidly induce pathological symptoms and enhance understanding of AD mechanisms.Neurofibrillary tangles and severe reactive astrogliosis were induced by injecting AAVDJ-EF1a-hTauP301L-EGFP and Adeno-GFAP-GFP viruses into the hippocampi of 5-month-old APP/PS1 mice.Three months post-injection,these mice exhibited pronounced astrogliosis,substantial amyloid-βplaque accumulation,extensiveneurofibrillarytangles,accelerated neuronal loss,elevated astrocytic GABA levels,and significant spatial memory deficits.Notably,these pathological features were less severe in AAVTauP301L-expressing APP/PS1 mice without augmented reactive astrogliosis.These findings indicate an exacerbating role of severe reactive astrogliosis in amyloid-βplaque and neurofibrillary tangle-associated pathology.The APP/PS1-TauP301L-Adeno mouse model provides a valuable tool for advancing therapeutic research aimed at mitigating the progression of AD.

关 键 词：Alzheimer's disease mouse model Neurofibrillary tangles Amyloid-βplaques Reactive astrogliosis Alzheimer’s disease pathology 

分 类 号：R749.16[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]