Marcel Levy Nogueira1, Stéphane Epelbaum2, Jean-Marc Steyaert3, Bruno Dubois4, Laurent Schwartz3. 1. Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Département de Neurologie, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France; Institut des Neurosciences Translationnelles de Paris (IHU-A-ICM), Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France; Laboratoire d'informatique (LIX), UMR 7161, Ecole Polytechnique, Université Paris-Saclay, Palaiseau, France. Electronic address: marcel.levy@psl.aphp.fr. 2. Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Département de Neurologie, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France; INSERM, CNRS, UMR-S975, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France; Sorbonne Universités, Université Pierre et Marie Curie, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France. 3. Laboratoire d'informatique (LIX), UMR 7161, Ecole Polytechnique, Université Paris-Saclay, Palaiseau, France. 4. Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Département de Neurologie, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France; Institut des Neurosciences Translationnelles de Paris (IHU-A-ICM), Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France; INSERM, CNRS, UMR-S975, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France; Sorbonne Universités, Université Pierre et Marie Curie, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France.
Abstract
INTRODUCTION: Extracellular accumulation of amyloid-β protein and intracellular accumulation of tau in brain tissues have been described in animal models of Alzheimer's disease (AD) and mechanical stress-based diseases of different mechanisms, such as traumatic brain injury (TBI), arterial hypertension (HTN), and normal pressure hydrocephalus (NPH). METHODS: We provide a brief overview of experimental models of TBI, HTN, and NPH showing features of tau-amyloid pathology, neuroinflammation, and neuronal loss. RESULTS: "Alzheimer-like" hallmarks found in these mechanical stress-based models were compared with AD features found in transgenic models. DISCUSSION: The goal of this review is, therefore, to build on current concepts of onset and progression of AD lesions. We point to the importance of accumulated mechanical stress in brain as an environmental and endogenous factor that pushes protein deposition and neuronal injury over the disease threshold. We further encourage the development of preventing strategies and drug screening based on mechanical stress models.
INTRODUCTION: Extracellular accumulation of amyloid-β protein and intracellular accumulation of tau in brain tissues have been described in animal models of Alzheimer's disease (AD) and mechanical stress-based diseases of different mechanisms, such as traumatic brain injury (TBI), arterial hypertension (HTN), and normal pressure hydrocephalus (NPH). METHODS: We provide a brief overview of experimental models of TBI, HTN, and NPH showing features of tau-amyloid pathology, neuroinflammation, and neuronal loss. RESULTS: "Alzheimer-like" hallmarks found in these mechanical stress-based models were compared with AD features found in transgenic models. DISCUSSION: The goal of this review is, therefore, to build on current concepts of onset and progression of AD lesions. We point to the importance of accumulated mechanical stress in brain as an environmental and endogenous factor that pushes protein deposition and neuronal injury over the disease threshold. We further encourage the development of preventing strategies and drug screening based on mechanical stress models.
Authors: Michael Krieg; Jan Stühmer; Juan G Cueva; Richard Fetter; Kerri Spilker; Daniel Cremers; Kang Shen; Alexander R Dunn; Miriam B Goodman Journal: Elife Date: 2017-01-18 Impact factor: 8.140