Neuropathological and behavioral features of an APP/PS1/MAPT (6xTg) transgenic model of Alzheimer’s disease

Abstract Alzheimer's disease is associated with various brain dysfunctions, including memory impairment, neuronal loss, astrocyte activation, amyloid-β plaques, and neurofibrillary tangles. Transgenic animal models of Alzheimer's disease have proven to be invaluable for the basic research...

Full description

Bibliographic Details
Main Authors: Sung Hyun Tag, Baeksun Kim, Jinhee Bae, Keun-A Chang, Heh-In Im
Format: Article
Language:English
Published: BMC 2022-06-01
Series:Molecular Brain
Subjects:
Online Access:https://doi.org/10.1186/s13041-022-00933-8
_version_ 1817976044163956736
author Sung Hyun Tag
Baeksun Kim
Jinhee Bae
Keun-A Chang
Heh-In Im
author_facet Sung Hyun Tag
Baeksun Kim
Jinhee Bae
Keun-A Chang
Heh-In Im
author_sort Sung Hyun Tag
collection DOAJ
description Abstract Alzheimer's disease is associated with various brain dysfunctions, including memory impairment, neuronal loss, astrocyte activation, amyloid-β plaques, and neurofibrillary tangles. Transgenic animal models of Alzheimer's disease have proven to be invaluable for the basic research of Alzheimer's disease. However, Alzheimer's disease mouse models developed so far do not fully recapitulate the pathological and behavioral features reminiscent of Alzheimer's disease in humans. Here, we investigated the neurobehavioral sequelae in the novel 6xTg mouse model of Alzheimer's disease, which was developed by incorporating human tau containing P301L mutation in the widely used 5xFAD mouse model of Alzheimer's disease. At 11-months-old, 6xTg mice displayed the core pathological processes found in Alzheimer's disease, including accumulation of amyloid-β plaque, extensive neuronal loss, elevated level of astrocyte activation, and abnormal tau phosphorylation in the brain. At 9 to 11-months-old, 6xTg mice exhibited both cognitive and non-cognitive behavioral impairments relevant to Alzheimer’s disease, including memory loss, hyperlocomotion, anxiety-like behavior, depression-like behavior, and reduced sensorimotor gating. Our data suggest that the aged 6xTg mouse model of Alzheimer's disease presents pathological and cognitive-behavioral features reminiscent of Alzheimer's disease in humans. Thus, the 6xTg mouse model of Alzheimer's disease may be a valuable model for studying Alzheimer’s disease-relevant non-cognitive behaviors.
first_indexed 2024-04-13T21:58:17Z
format Article
id doaj.art-726b6d512362420bbc3b042e0080e3a1
institution Directory Open Access Journal
issn 1756-6606
language English
last_indexed 2024-04-13T21:58:17Z
publishDate 2022-06-01
publisher BMC
record_format Article
series Molecular Brain
spelling doaj.art-726b6d512362420bbc3b042e0080e3a12022-12-22T02:28:11ZengBMCMolecular Brain1756-66062022-06-0115111310.1186/s13041-022-00933-8Neuropathological and behavioral features of an APP/PS1/MAPT (6xTg) transgenic model of Alzheimer’s diseaseSung Hyun Tag0Baeksun Kim1Jinhee Bae2Keun-A Chang3Heh-In Im4Convergence Research Center for Brain Science, Korea Institute of Science & Technology (KIST)Convergence Research Center for Brain Science, Korea Institute of Science & Technology (KIST)Convergence Research Center for Brain Science, Korea Institute of Science & Technology (KIST)Department of Pharmacology, College of Medicine, Gachon UniversityConvergence Research Center for Brain Science, Korea Institute of Science & Technology (KIST)Abstract Alzheimer's disease is associated with various brain dysfunctions, including memory impairment, neuronal loss, astrocyte activation, amyloid-β plaques, and neurofibrillary tangles. Transgenic animal models of Alzheimer's disease have proven to be invaluable for the basic research of Alzheimer's disease. However, Alzheimer's disease mouse models developed so far do not fully recapitulate the pathological and behavioral features reminiscent of Alzheimer's disease in humans. Here, we investigated the neurobehavioral sequelae in the novel 6xTg mouse model of Alzheimer's disease, which was developed by incorporating human tau containing P301L mutation in the widely used 5xFAD mouse model of Alzheimer's disease. At 11-months-old, 6xTg mice displayed the core pathological processes found in Alzheimer's disease, including accumulation of amyloid-β plaque, extensive neuronal loss, elevated level of astrocyte activation, and abnormal tau phosphorylation in the brain. At 9 to 11-months-old, 6xTg mice exhibited both cognitive and non-cognitive behavioral impairments relevant to Alzheimer’s disease, including memory loss, hyperlocomotion, anxiety-like behavior, depression-like behavior, and reduced sensorimotor gating. Our data suggest that the aged 6xTg mouse model of Alzheimer's disease presents pathological and cognitive-behavioral features reminiscent of Alzheimer's disease in humans. Thus, the 6xTg mouse model of Alzheimer's disease may be a valuable model for studying Alzheimer’s disease-relevant non-cognitive behaviors.https://doi.org/10.1186/s13041-022-00933-86xTgAlzheimer's diseaseCognitive impairmentSocial behaviorAnxietyDepression
spellingShingle Sung Hyun Tag
Baeksun Kim
Jinhee Bae
Keun-A Chang
Heh-In Im
Neuropathological and behavioral features of an APP/PS1/MAPT (6xTg) transgenic model of Alzheimer’s disease
Molecular Brain
6xTg
Alzheimer's disease
Cognitive impairment
Social behavior
Anxiety
Depression
title Neuropathological and behavioral features of an APP/PS1/MAPT (6xTg) transgenic model of Alzheimer’s disease
title_full Neuropathological and behavioral features of an APP/PS1/MAPT (6xTg) transgenic model of Alzheimer’s disease
title_fullStr Neuropathological and behavioral features of an APP/PS1/MAPT (6xTg) transgenic model of Alzheimer’s disease
title_full_unstemmed Neuropathological and behavioral features of an APP/PS1/MAPT (6xTg) transgenic model of Alzheimer’s disease
title_short Neuropathological and behavioral features of an APP/PS1/MAPT (6xTg) transgenic model of Alzheimer’s disease
title_sort neuropathological and behavioral features of an app ps1 mapt 6xtg transgenic model of alzheimer s disease
topic 6xTg
Alzheimer's disease
Cognitive impairment
Social behavior
Anxiety
Depression
url https://doi.org/10.1186/s13041-022-00933-8
work_keys_str_mv AT sunghyuntag neuropathologicalandbehavioralfeaturesofanappps1mapt6xtgtransgenicmodelofalzheimersdisease
AT baeksunkim neuropathologicalandbehavioralfeaturesofanappps1mapt6xtgtransgenicmodelofalzheimersdisease
AT jinheebae neuropathologicalandbehavioralfeaturesofanappps1mapt6xtgtransgenicmodelofalzheimersdisease
AT keunachang neuropathologicalandbehavioralfeaturesofanappps1mapt6xtgtransgenicmodelofalzheimersdisease
AT hehinim neuropathologicalandbehavioralfeaturesofanappps1mapt6xtgtransgenicmodelofalzheimersdisease