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P3‐088: THE AGING RHESUS MONKEY IS AN APPROPRIATE NEW ANIMAL MODEL FOR STUDYING THE ETIOLOGY AND TREATMENT OF TAU PATHOLOGY IN ASSOCIATION CORTEX
Author(s) -
Arnsten Amy F.T.,
Carlyle Becky C.,
Leslie Shan,
Preuss Todd M.,
Crimins Johanna L.,
Datta Dibyadeep,
Anita Huttner J.,
Dyck Christopher H.,
Rosene Douglas L.,
Nairn Angus C.,
Paspalas Constantinos
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.1444
Subject(s) - entorhinal cortex , neuroscience , tauopathy , cortex (anatomy) , pathology , biology , prefrontal cortex , senile plaques , cognition , psychology , hippocampus , alzheimer's disease , disease , medicine , neurodegeneration
cord. Proteins from homogenates of the different brain structures were separated using semi-native polyacrylamide gel electrophoresis. The different soluble tau oligomers were revealed on nitrocellulose blots using the tau antibody K9JA (DAKO). For MS, gel bands were excised, trypsin digested and peptides analyzed in LC-SRMmode using a triple quadrupole instrument. Presence of tau aggregates in the 3 structures was confirmed using HTRF (Cisbio). Tau phosphorylation and conformation was characterized using the antibodies AT8 and MC1, respectively. Spontaneous locomotor activity was evaluated over 90 min with 10-min recording interval. Results: Using the PS19 strain of tau transgenic mice, a time-dependent decrease of tau monomers with a corresponding increase in tau oligomers was observed in the cortex. A similar observation was made for the hippocampus. This time-dependent increase in tau oligomer formation was confirmed in the cortex and the hippocampus using HTRF. In both structures, tau aggregates start to increase at 6 months and show significantly higher amounts at 9 months. Tau aggregates are less prominent in the spinal cord. Phosphotau is clearly present at 9 months in all structures investigated, whereas the conformational antibody only slightly stained these regions. We observed no change in locomotor activity in this tau mutant strain at the ages tested. Conclusions: The PS19 tau mouse model shows progressive tau pathology in hippocampal and cortical structures and represents a useful model for drug discovery.