Mechanical stress models of Alzheimer's disease pathology

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.