Accelerated aging exacerbates a pre-existing pathology in a tau transgenic mouse model

Bodea, Liviu-Gabriel, Evans, Harrison Tudor, Van der Jeugd, Ann, Ittner, Lars M., Delerue, Fabien, Kril, Jillian, Halliday, Glenda, Hodges, John, Kiernan, Mathew C. and Goetz, Juergen (2017) Accelerated aging exacerbates a pre-existing pathology in a tau transgenic mouse model. Aging Cell, 16 2: 377-386. doi:10.1111/acel.12565

Author Bodea, Liviu-Gabriel
Evans, Harrison Tudor
Van der Jeugd, Ann
Ittner, Lars M.
Delerue, Fabien
Kril, Jillian
Halliday, Glenda
Hodges, John
Kiernan, Mathew C.
Goetz, Juergen
Title Accelerated aging exacerbates a pre-existing pathology in a tau transgenic mouse model
Journal name Aging Cell   Check publisher's open access policy
ISSN 1474-9726
Publication date 2017-01-01
Year available 2017
Sub-type Article (original research)
DOI 10.1111/acel.12565
Open Access Status DOI
Volume 16
Issue 2
Start page 377
End page 386
Total pages 10
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Subject 1302 Ageing
1307 Cell Biology
Abstract Age is a critical factor in the prevalence of tauopathies, including Alzheimer's disease. To observe how an aging phenotype interacts with and affects the pathological intracellular accumulation of hyperphosphorylated tau, the tauopathy mouse model pR5 (expressing P301L mutant human tau) was back-crossed more than ten times onto a senescence-accelerated SAMP8 background to establish the new strain, SApT. Unlike SAMP8 mice, pR5 mice are characterized by a robust tau pathology particularly in the amygdala and hippocampus. Analysis of age-matched SApT mice revealed that pathological tau phosphorylation was increased in these brain regions compared to those in the parental pR5 strain. Moreover, as revealed by immunohistochemistry, phosphorylation of critical tau phospho-epitopes (P-Ser202/P-Ser205 and P-Ser235) was significantly increased in the amygdala of SApT mice in an age-dependent manner, suggesting an age-associated effect of tau phosphorylation. Anxiety tests revealed that the older cohort of SApT mice (10 months vs. 8 months) exhibited a behavioural pattern similar to that observed for age-matched tau transgenic pR5 mice and not the SAMP8 parental mice. Learning and memory, however, appeared to be governed by the accelerated aging background of the SAMP8 strain, as at both ages investigated, SAMP8 and SApT mice showed a decreased learning capacity compared to pR5 mice. We therefore conclude that accelerated aging exacerbates pathological tau phosphorylation, leading to changes in normal behaviour. These findings further suggest that SApT mice may be a useful novel model in which to study the role of a complex geriatric phenotype in tauopathy.
Keyword Aging
Frontotemporal dementia
Geriatric condition
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID ACT900116
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
Centre for Ageing Dementia Research Publications
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Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
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