Multi-metric behavioral comparison of APPsw and P301L models for Alzheimer's disease: linkage of poorer cognitive performance to tau pathology in forebrain

Arendash, Gary W; Lewis, Jada; Leighty, Ralph E; McGowan, Eileen; Cracchiolo, Jennifer R; Hutton, Mike; Garcia, Marcos F

doi:10.1016/j.brainres.2004.02.081

Cited by 128Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeurological Disease Mechanisms and Treatments

Multi-metric behavioral comparison of APPsw and P301L models for Alzheimer's disease: linkage of poorer cognitive performance to tau pathology in forebrain

Arendash, Gary W, Lewis, Jada, Leighty, Ralph E, McGowan, Eileen, Cracchiolo, Jennifer R, Hutton, Mike, Garcia, Marcos F·2004·Brain Research

DOI 10.1016/j.brainres.2004.02.081

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Abstract

APPsw transgenic mice bearing the "Swedish" amyloid precursor protein (APP) mutation and JNPL3 transgenic mice bearing the P301L (Tau) mutation were compared to control non-transgenic (NT) mice in an extensive behavioral test battery administered between 5 and 8.5 months of age. APP mice were impaired in a variety of cognitive-based tasks prior to overt Abeta plaque development, making involvement of mutant APP overexpression and/or oligomeric Abeta assemblies most likely. Although Tau mice, as a group, were not impaired in any single behavioral measure, a collective assessment of behavioral measures through discriminant function analysis showed that Tau mice were impaired in overall behavioral (cognitive) performance. Moreover, correlation analyses involving Tau mice alone revealed linkage between poorer cognitive performance in all three water maze tasks and the number of neurofibrillary tangle (NFT)-containing neurons in neocortex and hippocampus. These findings indicate that: (1) APP mice show early and extensive cognitive impairment before evident Abeta deposition, and (2) the process or product of NFT formation in Tau mice is sufficient to deleteriously impact cognitive performance.

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“These spatial working memory deficits are generally accepted to be present across the rest of the life span for this model (Hsiao et al., 1996; Westerman et al., 2002; Arendash et al., 2004).”
From Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models (2014) · cites this paper as Arendash et al., 2004
In Tg2576, first presentation of cognitive deficits is at 5 months of age in spatial working memory.
“In the Tg2576 mouse (Hsiao et al., 1996), the first presentation of cognitive deficits is seen at 5 months of age in spatial working memory (Arendash et al., 2004).”
From Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models (2014) · cites this paper as Arendash et al., 2004

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Authors: Arendash, G. W., Lewis, J., Leighty, R. E., McGowan, E., Cracchiolo, J. R., Hutton, M., & Garcia, M. F.
Affiliations: University of South Florida (US)
Mayo Clinic (US)
Corresponding author: Arendash, Gary W
ORCID: Arendash, Gary W
Lewis, Jada
McGowan, Eileen
Cracchiolo, Jennifer R
Garcia, Marcos F
Venue: Brain Research
Publisher: Elsevier BV
Published: 2004-06
Volume: 1012
Issue: 1-2
Pages: 29-41
ISSN: 0006-8993 (ISSN-L)
DOI: 10.1016/j.brainres.2004.02.081
OpenAlex: W2111050644
Cited by: 127
References: 32
Citations by year: 2026: 2 · 2025: 2 · 2024: 6 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 4 · 2019: 4 · 2018: 2 · 2017: 5 · 2016: 6 · 2015: 8 · 2014: 7 · 2013: 6 · 2012: 9
FWCI: 4.59
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: 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 › Neurology › Neurological Disease Mechanisms and Treatments
Keywords: Alzheimer's disease, P301L tau mutation, cognitive impairment, amyloid precursor protein, amyloid-beta oligomers, neurofibrillary tangles, water maze, hippocampus, neocortex, behavioral phenotypes, discriminant function analysis
MeSH terms: Alzheimer Disease, Animals, Behavior, Animal, Cognition Disorders, Female, Mice, Inbred C57BL, Mice, Transgenic, Models, Neurological, Reaction Time, Prosencephalon, Amyloid beta-Protein Precursor, tau Proteins, Point Mutation, Maze Learning, Mice

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Multi-metric behavioral comparison of APPsw and P301L models for Alzheimer's disease: linkage of poorer cognitive performance to tau pathology in forebrain

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