The 5XFAD mouse model of Alzheimer’s disease displays age-dependent deficits in habituation to a novel environment

Smith, Sabrina; Hopp, Sarah C.

doi:10.1016/j.nbas.2023.100078

Cited by 9 publications

(5 citation statements)

References 34 publications

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“…In its fifth year, this workshop continues to provide a unique train- workshop. [41][42][43]50 This hands-on workshop is an annual event at JAX in Bar Har-…”

Section: Discussionmentioning

confidence: 99%

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Meeting report of the fifth annual workshop on Principles and Techniques for Improving Preclinical to Clinical Translation in Alzheimer's Disease Research

Sasner,

Onos,

Territo

et al. 2024

Alzheimer's & Dementia

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The fifth annual workshop on Principles and Techniques for Improving Preclinical Translation of Alzheimer's Disease Research was held in May 2023 at The Jackson Laboratory in Bar Harbor, Maine, USA. The workshop was established in 2018 to address training gaps in preclinical translational studies for Alzheimer's disease (AD). In addition to providing fundamental knowledge and hands‐on skills essential for executing rigorous in vivo studies that are designed to facilitate translation, each year the workshop aims to provide insight on state‐of‐the‐field technological advances and new resources including novel animal models, publicly available datasets, novel biomarkers, and new medical imaging tracers. This innovative and comprehensive workshop continues to deliver training for the greater AD research community in order to provide investigators and trainees with the knowledge and skillsets essential for enabling improved preclinical to clinical translation and accelerate the process of advancing safe and effective therapeutic interventions for AD.Highlights Translational research is not typically available as a course of study at academic institutions, yet there are fundamental skillsets and knowledge required to enable successful translation from preclinical experiments to clinical efficacy. It is important that there are resources and opportunities available to researchers planning preclinical translational experiments. Here we present proceedings from the fifth annual NIA‐sponsored workshop focused on enabling improved preclinical to clinical translation for Alzheimer's disease research that includes didactic lectures on state‐of‐the‐field approaches and hands‐on practicums for acquiring essential translational laboratory techniques.

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“…In its fifth year, this workshop continues to provide a unique train- workshop. [41][42][43]50 This hands-on workshop is an annual event at JAX in Bar Har-…”

Section: Discussionmentioning

confidence: 99%

“…Recent publications from previous workshop attendees also highlight the success of the approaches for improving preclinical to clinical translation, as well as the dissemination of resources including open access raw data available to the research community presented as part of this workshop. 41 , 42 , 43 , 50 …”

Section: Discussionmentioning

confidence: 99%

Meeting report of the fifth annual workshop on Principles and Techniques for Improving Preclinical to Clinical Translation in Alzheimer's Disease Research

Sasner,

Onos,

Territo

et al. 2024

Alzheimer's & Dementia

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“…Regarding anxiety, and from that point onward, few authors consistently reported no alterations in behaviour even in later stages of life [ 56 , 137 ]. Whereas a great number of reports have noted a gradual reduction in anxiety-like behaviour [ 40 , 41 , 43 , 44 , 47 , 55 , 58 , 59 , 104 , 127 , 149 , 150 ], a small number of studies have observed an increase in such behaviour [ 49 , 50 , 51 ]. Regarding depression, Medina-Vera and colleagues [ 45 ] mentioned depressive-like behaviour in 5xFAD mice from 5 months old with an age-related progression as the sucrose intake of the individuals was below the anhedonia criterion.…”

Section: The 5xfad Mouse Modelmentioning

confidence: 99%

“…The substantial variability and inconsistency in the results have raised numerous discussions regarding the reproducibility, the validity, and the reliability of those studies [ 154 , 157 , 158 , 159 ]. Although there are numerous well-established tests for assessing various behavioural aspects, minor methodological differences can dramatically impact the outcomes [ 150 ].…”

Section: Final Considerations and Forthcoming Directionsmentioning

confidence: 99%

Behaviour Hallmarks in Alzheimer’s Disease 5xFAD Mouse Model

Pádua,

Guil-Guerrero,

Lopes

2024

IJMS

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The 5xFAD transgenic mouse model widely used in Alzheimer’s disease (AD) research recapitulates many AD-related phenotypes with a relatively early onset and aggressive age-dependent progression. Besides developing amyloid peptide deposits alongside neuroinflammation by the age of 2 months, as well as exhibiting neuronal decline by the age of 4 months that intensifies by the age of 9 months, these mice manifest a broad spectrum of behavioural impairments. In this review, we present the extensive repertoire of behavioural dysfunctions in 5xFAD mice, organised into four categories: motor skills, sensory function, learning and memory abilities, and neuropsychiatric-like symptoms. The motor problems, associated with agility and reflex movements, as well as balance and coordination, and skeletal muscle function, typically arise by the time mice reach 9 months of age. The sensory function (such as taste, smell, hearing, and vision) starts to deteriorate when amyloid peptide buildups and neuroinflammation spread into related anatomical structures. The cognitive functions, encompassing learning and memory abilities, such as visual recognition, associative, spatial working, reference learning, and memory show signs of decline from 4 to 6 months of age. Concerning neuropsychiatric-like symptoms, comprising apathy, anxiety and depression, and the willingness for exploratory behaviour, it is believed that motivational changes emerge by approximately 6 months of age. Unfortunately, numerous studies from different laboratories are often contradictory on the conclusions drawn and the identification of onset age, making preclinical studies in rodent models not easily translatable to humans. This variability is likely due to a range of factors associated with animals themselves, housing and husbandry conditions, and experimental settings. In the forthcoming studies, greater clarity in experimental details when conducting behavioural testing in 5xFAD transgenic mice could minimise the inconsistencies and could ensure the reliability and the reproducibility of the results.

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“…Instead, the TgCRND8, PS2APP, and Tg‐ArcSwe models manifest both Aβ pathology and cognitive impairment almost simultaneously (Jankowsky & Zheng, 2017 ; Li et al., 2011 ). In the case of 5xFAD mice, it has been reported that Aβ accumulation starts at around 2 months (Youmans et al., 2012 ), but cognitive impairment is observed from ~5–6 months onwards (Smith & Hopp, 2023 ; Wei et al., 2016 ). Recently, pathophysiological changes including accumulation of Aβ and tau have been detected many years before the clinical manifestation of AD (Aisen et al., 2017 ; Palmqvist et al., 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Multi‐proteomic analyses of 5xFAD mice reveal new molecular signatures of early‐stage Alzheimer's disease

Lee,

Jang,

Lee

et al. 2024

Aging Cell

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An early diagnosis of Alzheimer's disease is crucial as treatment efficacy is limited to the early stages. However, the current diagnostic methods are limited to mid or later stages of disease development owing to the limitations of clinical examinations and amyloid plaque imaging. Therefore, this study aimed to identify molecular signatures including blood plasma extracellular vesicle biomarker proteins associated with Alzheimer's disease to aid early‐stage diagnosis. The hippocampus, cortex, and blood plasma extracellular vesicles of 3‐ and 6‐month‐old 5xFAD mice were analyzed using quantitative proteomics. Subsequent bioinformatics and biochemical analyses were performed to compare the molecular signatures between wild type and 5xFAD mice across different brain regions and age groups to elucidate disease pathology. There was a unique signature of significantly altered proteins in the hippocampal and cortical proteomes of 3‐ and 6‐month‐old mice. The plasma extracellular vesicle proteomes exhibited distinct informatic features compared with the other proteomes. Furthermore, the regulation of several canonical pathways (including phosphatidylinositol 3‐kinase/protein kinase B signaling) differed between the hippocampus and cortex. Twelve potential biomarkers for the detection of early‐stage Alzheimer's disease were identified and validated using plasma extracellular vesicles from stage‐divided patients. Finally, integrin α‐IIb, creatine kinase M‐type, filamin C, glutamine γ‐glutamyltransferase 2, and lysosomal α‐mannosidase were selected as distinguishing biomarkers for healthy individuals and early‐stage Alzheimer's disease patients using machine learning modeling with approximately 79% accuracy. Our study identified novel early‐stage molecular signatures associated with the progression of Alzheimer's disease, thereby providing novel insights into its pathogenesis.

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The 5XFAD mouse model of Alzheimer’s disease displays age-dependent deficits in habituation to a novel environment

Cited by 9 publications

References 34 publications

Meeting report of the fifth annual workshop on Principles and Techniques for Improving Preclinical to Clinical Translation in Alzheimer's Disease Research

Meeting report of the fifth annual workshop on Principles and Techniques for Improving Preclinical to Clinical Translation in Alzheimer's Disease Research

Behaviour Hallmarks in Alzheimer’s Disease 5xFAD Mouse Model

Multi‐proteomic analyses of 5xFAD mice reveal new molecular signatures of early‐stage Alzheimer's disease

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