title: Lack of tau proteins rescues neuronal cell death and decreases amyloidogenic processing of APP in APP/PS1 mice.
abstract: Lack of tau expression has been reported to protect against excitotoxicity and to prevent memory deficits in mice expressing mutant amyloid precursor protein (APP) identified in familial Alzheimer disease. In APP mice, mutant presenilin 1 (PS1) enhances generation of Aβ42 and inhibits cell survival pathways. It is unknown whether the deficient phenotype induced by concomitant expression of mutant PS1 is rescued by absence of tau. In this study, we have analyzed the effect of tau deletion in mice expressing mutant APP and PS1. 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 and synaptic loss in APP/PS1/tau(+/+) mice were rescued in the APP/PS1/tau(-/-) mice. The amyloid plaque burden was decreased by roughly 50% in the cortex and the spinal cord of the APP/PS1/tau(-/-) mice. The levels of soluble and insoluble Aβ40 and Aβ42, and the Aβ42/Aβ40 ratio were reduced in APP/PS1/tau(-/-) mice. Levels of phosphorylated APP, of β-C-terminal fragments (CTFs), and of β-secretase 1 (BACE1) were also reduced, suggesting that β-secretase cleavage of APP was reduced in APP/PS1/tau(-/-) mice. Our results indicate that tau deletion had a protective effect against amyloid induced toxicity even in the presence of mutant PS1 and reduced the production of Aβ.
authors.affiliation: Laboratory of Histology, Neuroanatomy, and Neuropathology, Université Libre de Bruxelles, 808 Route de Lennik, Brussels, Belgium.
authors.forename: Karelle
authors.initials: K
authors.lastname: Leroy
authors.forename: Kunie
authors.initials: K
authors.lastname: Ando
authors.forename: Vincent
authors.initials: V
authors.lastname: Laporte
authors.forename: Robert
authors.initials: R
authors.lastname: Dedecker
authors.forename: Valérie
authors.initials: V
authors.lastname: Suain
authors.forename: Michèle
authors.initials: M
authors.lastname: Authelet
authors.forename: Céline
authors.initials: C
authors.lastname: Héraud
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pierrot
authors.forename: Zehra
authors.initials: Z
authors.lastname: Yilmaz
authors.forename: Jean-Noël
authors.initials: JN
authors.lastname: Octave
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Brion
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D016923:Cell Death; D049229:Dendritic Spines / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D008570:Memory, Short-Term; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D010766:Phosphorylation; D010769:Phosphothreonine / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D053764:Presenilin-1 / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012995:Solubility; D016019:Survival Analysis; D013569:Synapses / Q000473:pathology / Q000648:ultrastructure; D016875:tau Proteins / Q000172:deficiency* / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D016875:tau Proteins; D010769:Phosphothreonine; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse