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Cited by 145Alzheimer's disease research and treatmentsParkinson's Disease Mechanisms and TreatmentsDementia and Cognitive Impairment Research

Motor and cognitive deficits in aged tau knockout mice in two background strains

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Lei, Peng, Ayton, Scott, Moon, Steve, Zhang, Qihao, Volitakis, Irene, Finkelstein, David I, Bush, Ashley I·2014·Molecular Neurodegeneration
DOI 10.1186/1750-1326-9-29PMC PMC4141346
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Abstract

BACKGROUND: We recently reported that Parkinsonian and dementia phenotypes emerge between 7-12 months of age in tau-/- mice on a Bl6/129sv mixed background. These observations were partially replicated by another group using pure Bl6 background tau-/- mice, but notably they did not observe a cognitive phenotype. A third group using Bl6 background tau-/- mice found cognitive impairment at 20-months of age. RESULTS: To reconcile the observations, here we considered the genetic, dietary and environmental variables in both studies, and performed an extended set of behavioral studies on 12-month old tau+/+, tau+/-, and tau-/- mice comparing Bl6/129sv to Bl6 backgrounds. We found that tau-/- in both backgrounds exhibited reduced tyrosine hydroxylase-positive nigral neuron and impaired motor function in all assays used, which was ameliorated by oral treatment with L-DOPA, and not confounded by changes in body weight. Tau-/- in the C57BL6/SV129 background exhibited deficits in the Y-maze cognition task, but the mice on the Bl6 background did not. CONCLUSIONS: These results validate our previous report on the neurodegenerative phenotypes of aged tau-/- mice, and show that genetic background may impact the extent of cognitive impairment in these mice. Therefore excessive lowering of tau should be avoided in therapeutic strategies for AD.

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  • Tau-mediated neurodegeneration arises from multiple pathological mechanisms including loss of normal function, gain of toxic function, aggregation, and mislocalization.

    “Tau-mediated neurodegeneration arises from multiple pathological mechanisms, including loss of normal function [37–42], gain of toxic function [43–46], aggregation [44, 47–49], and mislocalization [50–52].”

    From Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease (2026) · cites this paper as [37]

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Cited by

Sorted by citations

Authors
Lei, P., Ayton, S., Moon, S., Zhang, Q., Volitakis, I., Finkelstein, D. I., & Bush, A. I.
Affiliations
  • The University of Melbourne (AU)
  • Jinan University (CN)
Corresponding author
Bush, Ashley I
ORCID
Venue
Molecular Neurodegeneration
Publisher
Springer Science and Business Media LLC
Published
2014-08-14
Volume
9
Issue
1
Pages
29-29
ISSN
1750-1326 (ISSN-L)
DOI
10.1186/1750-1326-9-29
PMC
PMC4141346
OpenAlex
W2129733921
Cited by
145
References
9
Citations by year
2026: 10 · 2025: 7 · 2024: 9 · 2023: 15 · 2022: 13 · 2021: 17 · 2020: 19 · 2019: 8 · 2018: 11 · 2017: 12 · 2016: 15 · 2015: 8 · 2014: 1
FWCI
8.00
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Molecular Neurodegeneration (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
Funders
  • Strong
  • Medical Research Council
  • Australian Research Council
  • National Health and Medical Research Council
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
tau knockout mice, Parkinson's disease, Alzheimer's disease, motor impairment, cognitive impairment, genetic background effects, C57BL/6 mice, nigral neurons, tyrosine hydroxylase, L-DOPA, Y-maze, aged mice, neurodegeneration
MeSH terms
Aging, Animals, Behavior, Animal, Cognition Disorders, Diet, Disease Models, Animal, Environment, Female, Male, Mice, Inbred C57BL, Nerve Degeneration, Phenotype, Substantia Nigra, tau Proteins, Mice, Knockout, Genetic Predisposition to Disease, Mice

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