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O1‐02‐04: Tau deletion rescues neuronal death in APP/PS1 mice
Author(s) -
Leroy Karelle,
Ando Kunie,
Laporte Vincent,
Dedecker Robert,
Suain Valérie,
Authelet Michèle,
Héraud Céline,
Pierrot Nathalie,
Yilmaz Zehra,
Octave JeanNoël,
Brion JeanPierre
Publication year - 2012
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.2012.05.211
Subject(s) - mutant , hippocampus , amyloid precursor protein , immunocytochemistry , neuroscience , microbiology and biotechnology , spinal cord , blot , medicine , endocrinology , biology , chemistry , alzheimer's disease , biochemistry , gene , disease
Background:Recent results have shown that lack of tau expression protects against excitotoxicity and prevents the development of memory deficits in mice overexpressing mutant APP. In these mice, mutant PS1 enhances generation of Aß42, and inhibits cell survival pathways. It is however unknown if the deficient phenotype induced by concomitant expression of mutant PS1 is also rescued by absence of tau. Methods: To investigate this issue, we have analyzed the effect of tau deletion on the behavioural deficits and the development of pathology in mice expressing mutant forms of APP and PS1. APP/PS1/tau+/+ mice were compared to APP/PS1/tau-/-, tau-/and tau+/+ mice. Motor deficits and spatial memory were analyzed with the rotarod test and the Y maze. Neuronal death was analyzed at 12 months using the optical fractionator method. The amyloid load was analyzed by immunocytochemistry, western blotting and ELISA. Results: Although APP/PS1/tau+/+ mice had a reduced survival, developed spatial memory deficits at 6 months and motor impairments at 12 months, these deficits were rescued in APP/PS1/tau-/mice. Neuronal loss observed in the hippocampus and the spinal cord of APP/PS1/tau+/+micewas not observed in the APP/PS1/tau-/mice. The amyloid plaque burden was decreased in the cortex and the spinal cord of the APP/PS1/tau-/mice compared to APP/PS1 mice. The levels of soluble and insoluble Aß38, Aß40, Aß42, and the Aß42/Aß40 ratio were reduced in APP/PS1/tau-/mice. Levels of phosphorylated APP, of ß-CTFs and levels of BACE1 were also reduced, suggesting that ß-secretase cleavage of APP was reduced in APP/PS1/tau-/mice.Conclusions:Our results indicate that tau deletion had a protective effect against amyloid induced toxicity also in presence of a mutant PS1 protein and led to a reduction of the production of Aß in an APP/PS1 transgenic model.