Open AccessAccelerated aging exacerbates a pre‐existing pathology in a tau transgenic mouse model
Author(s) -
Bodea LiviuGabriel,
Evans Harrison Tudor,
Van der Jeugd Ann,
Ittner Lars M.,
Delerue Fabien,
Kril Jillian,
Halliday Glenda,
Hodges John,
Kiernan Mathew C.,
Götz Jürgen
Publication year - 2017
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12565
Subject(s) - tauopathy , genetically modified mouse , hippocampus , biology , pathological , transgene , phosphorylation , senescence , phenotype , amygdala , neuroscience , psychology , medicine , disease , microbiology and biotechnology , genetics , gene , neurodegeneration
Summary 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 pR 5 (expressing P301L mutant human tau) was back‐crossed more than ten times onto a senescence‐accelerated SAMP 8 background to establish the new strain, SA pT. Unlike SAMP 8 mice, pR 5 mice are characterized by a robust tau pathology particularly in the amygdala and hippocampus. Analysis of age‐matched SA pT mice revealed that pathological tau phosphorylation was increased in these brain regions compared to those in the parental pR 5 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 SA pT mice in an age‐dependent manner, suggesting an age‐associated effect of tau phosphorylation. Anxiety tests revealed that the older cohort of SA pT mice (10 months vs. 8 months) exhibited a behavioural pattern similar to that observed for age‐matched tau transgenic pR 5 mice and not the SAMP 8 parental mice. Learning and memory, however, appeared to be governed by the accelerated aging background of the SAMP 8 strain, as at both ages investigated, SAMP 8 and SA pT mice showed a decreased learning capacity compared to pR 5 mice. We therefore conclude that accelerated aging exacerbates pathological tau phosphorylation, leading to changes in normal behaviour. These findings further suggest that SA pT mice may be a useful novel model in which to study the role of a complex geriatric phenotype in tauopathy.