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Amyloid precursor protein reduction enhances the formation of neurofibrillary tangles in a mutant tau transgenic mouse model.
Neurobiol Aging. 2017 07; 55:202-212.NA

Abstract

Alzheimer's disease is characterized by the presence of 2 neuropathological lesions: neurofibrillary tangles, composed of tau proteins which are highly phosphorylated and phosphorylated on uncommon sites, and amyloid plaques, containing the Aβ peptides generated from the amyloid precursor protein (APP). Reduction of some APP proteolytic derivatives in Alzheimer's disease such as sAPPα fragment has been reported and sAPPα has been shown to affect tau phosphorylation. To investigate in vivo the effect of absence of APP protein and its fragments on tau phosphorylation and the formation of neurofibrillary tangles, we have generated mice deleted for APP gene and overexpressing a human mutant tau protein and developing neurofibrillary tangles (APPKOTg30 mice). These APPKOTg30 mice showed more severe motor and cognitive deficits, increased tau phosphorylation, increased load of neurofibrillary tangles, and increased p25/35 ratio in the brain, compared with Tg30 mice. These data suggest that APP and/or its proteolytic derivatives interfere with the formation of neurofibrillary tangles in a transgenic mouse model that will be useful for investigating the relationship between APP and tau.

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Authors+Show Affiliations

Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, Brussels, Belgium.

Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, Brussels, Belgium.

Institute of Neurosciences, Université catholique de Louvain, Brussels, Belgium.

Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, Brussels, Belgium.

Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, Brussels, Belgium.

Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, Brussels, Belgium.

Universite de Lille, INSERM, CHU-Lille, UMR-S 1172, LabEx DISTALZ, Lille, France.

Institute of Neurosciences, Université catholique de Louvain, Brussels, Belgium.

Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, Brussels, Belgium.

Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, Brussels, Belgium. Electronic address: kleroy@ulb.ac.be.

MeSH

Alzheimer DiseaseAmyloid beta-Protein PrecursorAnimalsCognitive DysfunctionDisease Models, AnimalMice, TransgenicMutationNeurofibrillary TanglesPhosphorylationtau Proteins

Pub Type(s)

Journal Article

Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28464981

Citation

Vanden Dries, Virginie, et al. "Amyloid Precursor Protein Reduction Enhances the Formation of Neurofibrillary Tangles in a Mutant Tau Transgenic Mouse Model." Neurobiology of Aging, vol. 55, 2017, pp. 202-212.

Vanden Dries V, Stygelbout V, Pierrot N, et al. Amyloid precursor protein reduction enhances the formation of neurofibrillary tangles in a mutant tau transgenic mouse model. Neurobiol Aging. 2017;55:202-212.

Vanden Dries, V., Stygelbout, V., Pierrot, N., Yilmaz, Z., Suain, V., De Decker, R., Buée, L., Octave, J. N., Brion, J. P., & Leroy, K. (2017). Amyloid precursor protein reduction enhances the formation of neurofibrillary tangles in a mutant tau transgenic mouse model. Neurobiology of Aging, 55, 202-212. https://doi.org/10.1016/j.neurobiolaging.2017.03.031

Vanden Dries V, et al. Amyloid Precursor Protein Reduction Enhances the Formation of Neurofibrillary Tangles in a Mutant Tau Transgenic Mouse Model. Neurobiol Aging. 2017;55:202-212. PubMed PMID: 28464981.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Amyloid precursor protein reduction enhances the formation of neurofibrillary tangles in a mutant tau transgenic mouse model. AU - Vanden Dries,Virginie, AU - Stygelbout,Virginie, AU - Pierrot,Nathalie, AU - Yilmaz,Zehra, AU - Suain,Valérie, AU - De Decker,Robert, AU - Buée,Luc, AU - Octave,Jean-Noël, AU - Brion,Jean-Pierre, AU - Leroy,Karelle, Y1 - 2017/04/05/ PY - 2016/11/14/received PY - 2017/02/01/revised PY - 2017/03/28/accepted PY - 2017/5/4/pubmed PY - 2017/11/29/medline PY - 2017/5/4/entrez KW - Alzheimer's disease KW - Amyloid precursor protein KW - Neurofibrillary tangles KW - Transgenic mouse SP - 202 EP - 212 JF - Neurobiology of aging JO - Neurobiol Aging VL - 55 N2 - Alzheimer's disease is characterized by the presence of 2 neuropathological lesions: neurofibrillary tangles, composed of tau proteins which are highly phosphorylated and phosphorylated on uncommon sites, and amyloid plaques, containing the Aβ peptides generated from the amyloid precursor protein (APP). Reduction of some APP proteolytic derivatives in Alzheimer's disease such as sAPPα fragment has been reported and sAPPα has been shown to affect tau phosphorylation. To investigate in vivo the effect of absence of APP protein and its fragments on tau phosphorylation and the formation of neurofibrillary tangles, we have generated mice deleted for APP gene and overexpressing a human mutant tau protein and developing neurofibrillary tangles (APPKOTg30 mice). These APPKOTg30 mice showed more severe motor and cognitive deficits, increased tau phosphorylation, increased load of neurofibrillary tangles, and increased p25/35 ratio in the brain, compared with Tg30 mice. These data suggest that APP and/or its proteolytic derivatives interfere with the formation of neurofibrillary tangles in a transgenic mouse model that will be useful for investigating the relationship between APP and tau. SN - 1558-1497 UR - https://www.unboundmedicine.com/medline/citation/28464981/Amyloid_precursor_protein_reduction_enhances_the_formation_of_neurofibrillary_tangles_in_a_mutant_tau_transgenic_mouse_model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-4580(17)30114-8 DB - PRIME DP - Unbound Medicine ER -