Amyloid-induced Tauopathy contributes to synaptic and cognitive deficits in a transgenic model for Alzheimer's disease
(2014) Alzheimer’s Association International Conference (AAIC) 2014 — Location: Copenhagen, Denmark (12.July.2014)
Files
document.pdf
Restricted Access - Adobe PDF
- 54.77 KB
Details
- Authors
- Abstract
- Background: Brains of Alzheimer’s disease patients are characterized by the presence of amyloid plaques and neurofibrillary tangles, as diagnostic hallmarks. Mouse models combining amyloidosis and Tauopathy and their parental counterparts are important tools to further investigate the interplay of abnormal Abeta and Tau species in pathogenesis, synaptic and neuronal dysfunction and cognitive decline. Methods: Crosses of APP/PS1 mice with 5 EOFAD mutations (5xFAD) and TauP301S (PS19) transgenic mice - denoted F+/T+ mice - were generated and phenotypically compared to their respective parental strains - denoted F+/T- and T+/F- respectively. Results: Tau pathology was invariably and very robustly aggravated in hippocampal and cortical brain regions in F+/T+ mice compared to the parental T+ mice. In contrast, amyloidosis was unaltered compared to the parental F+/T- mice. Most importantly, F+/T+ displayed aggravated cognitive deficits in a hippocampus-dependent spatial navigation task, compared to the parental F+/T- strain, while parental T+/F- mice did not display cognitive impairment. In F+/T+ mice basal synaptic transmission was impaired compared to non-transgenic mice and the parental strains. Finally, F+/T+ mice displayed a significant hippocampal atrophy compared to non-transgenic mice, in contrast to the parental strains. Conclusions: Our data indicate for the first time that pathological Abeta species induced changes in Tau contribute to cognitive deficits correlating with synaptic deficits and hippocampal atrophy in an AD model. These data lend further support to an executive role of Tau in the pathogenetic process of AD and to the amyloid cascade hypothesis with a role of pathological Abeta species as initiator and pathological Tau species as executor.
- Affiliations
Citations
Stancu, I.-C., Ris, L., Barbosa de Vasconcelos, B., Marinangeli, C., Goeminne, L., Laporte, V., El Haylani, L., Couturier, J., Schakman, O., Gailly, P., Pierrot, N., Kienlen-Campard, P., Octave, J.-N., & Dewachter, I. (2014). Amyloid-induced Tauopathy contributes to synaptic and cognitive deficits in a transgenic model for Alzheimer’s disease. Alzheimer’s & Dementia, 10(4 (Suppl)), P315. https://doi.org/10.1016/j.jalz.2014.05.268 (Original work published 2014)