Reduction in open field activity in the absence of memory deficits in the AppNL−G−F knock-in mouse model of Alzheimer’s disease

Whyte, Lauren S.; Hemsley, Kim M.; Lau, Adeline A.; Hassiotis, Sofia; Saito, Takashi; Saido, Takaomi C.; Hopwood, John J.; Sargeant, Timothy J.

doi:10.1016/j.bbr.2017.09.006

Cited by 88Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchMemory and Neural Mechanisms

Reduction in open field activity in the absence of memory deficits in the AppNL−G−F knock-in mouse model of Alzheimer’s disease

Whyte, Lauren S., Hemsley, Kim M., Lau, Adeline A., Hassiotis, Sofia, Saito, Takashi, Saido, Takaomi C., Hopwood, John J., Sargeant, Timothy J.·2018·Behavioural Brain Research

DOI 10.1016/j.bbr.2017.09.006

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Abstract

The recent development of knock-in mouse models of Alzheimer's disease provides distinct advantages over traditional transgenic mouse models that rely on over-expression of amyloid precursor protein. Two such knock-in models that have recently been widely adopted by Alzheimer's researchers are the App NL-F and App NL-G-F mice. This study aimed to further characterise the behavioural phenotype and amyloid plaque distribution of App NL-G-F/NL-G-F (C57BL/6J background) mice at six-months of age. An attempt to replicate a previous study that observed deficits in working memory in the Y-maze, showed no difference between App NL-G-F/NL-G-F and wild-type mice. Further assessment of these mice using the novel object recognition test and Morris water maze also revealed no differences between App NL-G-F/NL-G-F and wild-type mice. Despite a lack of demonstrated cognitive deficits, we report a reduction in locomotor/exploratory activity in an open field. Histological examination of App NL-G-F/NL-G-F mice showed widespread distribution of amyloid plaques at this age. We conclude that whilst at six-months of age, memory deficits are not sufficiently robust to be replicated in varying environments, amyloid plaque burden is significant in App NL-G-F/NL-G-F knock-in brain.

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Findings on Morris water maze deficits in AppNL-G-F/NL-G-F mice are inconsistent: two groups reported no obvious deficits up to 12 months of age, whereas another reported robust deficits at 6 months of age.
“for example, in the MWM task, two groups have reported that AppNL-G-F/NL-G-F mice develop no obvious deficits in spatial learning and memory up to 12 months of age [21, 23], whereas another reported robust learning and memory deficits in AppNL-G-F/NL-G-F mice at 6 months of age [12].”
From Amyloid-β plaque formation and reactive gliosis are required for induction of cognitive deficits in App knock-in mouse models of Alzheimer’s disease (2019) · cites this paper as [23]
There was no effect of genotype on spontaneous alternations in the males.
“In contrast, there was no effect of genotype on spontaneous alternations in the males in our study, similar to the lack if genotype differences reported previously in the Y maze41.”
From Integrated analysis of behavioral, epigenetic, and gut microbiome analyses in AppNL-G-F, AppNL-F, and wild type mice (2021) · cites this paper as [41]
Humanized App knockin (KI) and APP transgenic mouse models mimic certain aspects of AD pathogenesis, including progressive amyloidosis, gliosis, and neuroinflammation, as well as network hyperexcitability and cognitive impairment, albeit to different degrees of severity across models and paradigms.
“Humanized App knockin (KI) and APP transgenic mouse models mimic certain aspects of AD pathogenesis, including progressive amyloidosis, gliosis, and neuroinflammation, as well as network hyperexcitability and cognitive impairment, albeit to different degrees of severity across models and paradigms.15-27”
From Machine learning reveals prominent spontaneous behavioral changes and treatment efficacy in humanized and transgenic Alzheimer's disease models (2024) · cites this paper as [18]

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Authors: Whyte, L. S., Hemsley, K. M., Lau, A. A., Hassiotis, S., Saito, T., Saido, T. C., Hopwood, J. J., & Sargeant, T. J.
Affiliations: South Australian Health and Medical Research Institute (AU)
RIKEN Center for Brain Science (JP)
Corresponding author: Sargeant, Timothy J.
ORCID: Whyte, Lauren S.
Hemsley, Kim M.
Lau, Adeline A.
Saito, Takashi
Saido, Takaomi C.
Sargeant, Timothy J.
Venue: Behavioural Brain Research
Publisher: Elsevier BV
Published: 2018-01
Volume: 336
Pages: 177-181
ISSN: 0166-4328 (ISSN-L)
DOI: 10.1016/j.bbr.2017.09.006
OpenAlex: W2752717680
Cited by: 88
References: 21
Citations by year: 2026: 6 · 2025: 18 · 2024: 16 · 2023: 8 · 2022: 7 · 2021: 10 · 2020: 9 · 2019: 9 · 2018: 3 · 2017: 2
FWCI: 4.65
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Behavioural Brain Research (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: Alzheimer's disease, amyloid plaques, open field behavior, locomotor activity, exploratory behavior, memory impairment, working memory, novel object recognition, Morris water maze, behavioral phenotypes, amyloid precursor protein
MeSH terms: Alzheimer Disease, Animals, Behavior, Animal, Brain, Disease Models, Animal, Exploratory Behavior, Male, Memory Disorders, Memory, Short-Term, Mice, Inbred C57BL, Mice, Transgenic, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Maze Learning, Mice, Gene Knock-In Techniques, Plaque, Amyloid, Cognitive Dysfunction

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Reduction in open field activity in the absence of memory deficits in the AppNL−G−F knock-in mouse model of Alzheimer’s disease

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