Alzheimerʹs disease-related changes in diseases characterized by elevation of intracranial or intraocular pressure

In this review, we focus on the coexistence of Alzheimerʹs disease-related changes in brain diseases, such as normal pressure hydrocephalus and traumatic brain injury, and in glaucoma at the level of the retinal ganglion cells. This is a group of diseases that affect central nervous system tissue and are characterized by elevation of intracranial or intraocular pressure and/or local shear stress and strain. In considering possible mechanisms underlying Alzheimer-type changes in these diseases, we briefly summarize recent evidence indicating that caspase activation and abnormal processing of β-amyloid precursor protein, which are important events in Alzheimerʹs disease, may play a role both in glaucoma and following traumatic brain injury. With regard to normal pressure hydrocephalus, evidence suggests that changes in cerebrospinal fluid circulatory dynamics ultimately may result in reduced clearance of neurotoxins, such as β-amyloid peptides and tau protein, that play a role in the pathogenesis of Alzheimerʹs disease. Data presented in this review could be interpreted to suggest that Alzheimer-type changes in these diseases may result at least in part from exposure of central nervous system tissue to increased levels of mechanical stress. Evidence for such a relationship is of major importance because it may support an association between elevated mechanical load and the development of Alzheimer-type lesions. Further studies are warranted, however, especially to elucidate the role of elevated mechanical forces in Alzheimerʹs disease neuropathogenesis.