Critical Review on the Relationship between Glaucoma and Alzheimer's Disease

Abstract

two distinct pathologies, despite similar pathophysiology and demographic distribution. Both diseases are neurodegenerative, chronic and progressive in nature, with irreversible neuronal cell loss. Furthermore, both POAG and AD disease primarily affect the elderly, with a strongly age-dependent incidence. The progressive debilitating course of both diseases has tremendous implications on an aging population [1]. For years Glaucoma has been associated with high IOP [2], although scientists had accepted this etiology with caution, since it was known that POAG could develop in subjects with normal or even low IOP. In fact, one out of three POAG patients has normotensive or low tension glaucoma [3]. This observation has led the scientific community to look for other possible causes of this slowly debilitating pathogenesis.The hallmark of neurodegenerative diseases is the death of specific neuron populations, and of those other neurons that are inter-connected and depend for their survival on the inputs from the main population (trans-synaptic degeneration). In Parkinson's disease accumulation of alfa-synuclein [4] causes the degeneration of dopaminergic neurons of the substantia nigra, in the midbrain, thus leading to the classic symptoms of Parkinson's such as tremor, akinesia, bradykinesia, and stiffness [5]. In AD there is a loss of neurons in the cerebral cortex and certain subcortical regions. This loss results in gross atrophy of the affected regions, including degeneration in the temporal lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus [6]. Both amyloid plaques and neurofibrillary tangles are AbstractA third of people affected by primary open angle glaucoma (POAG) have normal or even low intraocular pressure (IOP), such as in the case of normotensive glaucoma and low pressure glaucoma. Therefore, high IOP, while remaining the most important risk factor for POAG development, is not the only one. POAG has been recognized to belong to the class of neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's, and several recent studies have suggested possible links between Alzheimer's and glaucoma both from an epidemiological and a pathogenetic point of view. In fact, several pathogenetic factors are common between the two diseases: the diffuse axonal degeneration of ganglion cells, the presence of specific markers (such as amyloid-β) in the aqueous humor, the activation of caspases and the abnormal processing of amyloid precursor protein in retinal ganglion cells, the reduction of the intracranial pressure of the cerebrospinal fluid, the mutations of the gene that encodes for optineurine. Conflicting data have been reported concerning apolipoprotein E. Finally, numerous publications affirm the utility of molecules traditionally used in the treatment of neurodegenerative diseases (e.g. forskolin, L-carnosine, homotaurine, folic acid, acetylcholinesterase inhibitors, antioxidant vitamins, glatiramer acetate, etc.) also in the treatment of glaucoma.In the present research we ana...