Title : Could We See Alzheimer’s Disease Through the Eye?
Abstract:
One of the most common and prevalent neurodegenerative disorders are Alzheimer's and Dementia which are considered significant causes of mortality and morbidity in today’s society particularly among the elderly population.(Erkkinen, Kim et al. 2018)The etiologic and pathophysiologic factors of neuro-degenerative disorders are still complicated and unrecognized. In last decade the overall mortality rate for deaths cause by dementia and Alzheimer's disease has been generally increasing year-on-year. One of concerning statistics reported by Office for National Statistics which indicates approximately 52% of increase in amount of people who diagnosed with dementia. Indeed it is very threatening statistics in deaths of any health condition. From statistical point of view such huge increase on these disorders make and urgent need to understand the mechanisms behind the onset and progression of these heterogeneous diseases( Fig 1). Currently diagnosing Alzheimer’s disease is also challenging due to lack of biomarkers. One of the pathological factors of Alzheimer’s disease include the accumulation of proteins such as hyper phosphorylated tau and amyloid protein in hippocampal areas of the brain. The detection of these pathological biomarkers are conducted either by performing cerebrospinal fluid analysis, brain imaging or post-mortem brain tissues under microscope. However, these methods are not easily accessible and largely available due to different reasons. These include challenges in collecting certain samples, lack of post-mortem tissues and high-cost of experiment.(Guidoboni, Sacco et al. 2020)
Many researches and investigations on neurodegenerative disorders suggest that when neurodegeneration process starts in the brain, this alteration can also influence the eyes. In fact human eye is directly linked to the brain via the optic nerve.The brain is the main area of our eyes and our visual system which mainly consist of optic nerve and retina and these two main part of eyes one of the brain tissues. Alternatively when there is a damage on different brain cells,these atrophic changes also affect to the function of retina. Human eye illustrates a very spectacular window to the brain which can be easily examined by ocular imaging. Researches also indicate that individuals suffering from neurological disorders and several other neurological diseases often exhibit significant structural and vascular changes in the visual field.(T Reed, Behar-Cohen et al. 2017)In fact vascular changes in the eye is also associated vascular changes in the brain (Heringa, Bouvy et al. 2013)This association is not surprising because the eye as an organ is a protrusion of the brain and the origin of our visual system starts from brain .In addition the ophthalmic artery plays one of the main role in brain as well as providing eye with blood. Retina also responsible for various characteristics with the cerebral microvasculature and the neurons of the central nervous system .
Figure 1: The cause of death groups used here are based on a list developed by the WHO, modified for use in England and Wales. Source: Office for National Statistics
According to various research many patients diagnosed with Alzheimer's report impairments with visual symptoms. (Fiorio, Tinazzi et al. 2006)These facts indeed had been an increased interest in finding the specific peculiar optholmalogic biomarkers. In fact, the contribution of ocular measurements is very wide in terms of early diagnosing many morbid diseases including heart,stroke.The usage of eye measurements have been considered as a significant tool of biomarkers for the prediction of neurodegenerative disorders. Another reason is that the eye is the only place in the human body where structural and functional vascular features can be observed and measured easily and non-invasively down to the capillary level (Harris et al., 2003; Weinreb and Harris, 2009).
Last decade the relationship between neurodegenerative disorders and eye had been n main interest area of scientists. Recent studies have revealed that there are many similarities linking glaucoma and AD. Studies suggest that Alzheimer's Disease and glaucoma should be considered age-related neurodegenerative diseases, bearing in mind the common features of both diseases, including risk factors and pathophysiological mechanisms.(Mancino, Martucci et al. 2018) Furthermore, recent studies suggest that at the molecular genetic level, AD and age-related macular degeneration (AMD) share common, pathological signaling defects and disease mechanisms.(Biscetti, Luchetti et al. 2017) There is increasing evidence that β-amyloid, the main component of senile plaques that characterize AD, is also a vital component and a hallmark of AMD.(Frost, Guymer et al. 2016)
One thing is that AMD is a retinal disease and affect mostly retina , research suggest that AD also damages brain cells as well as the retina. Both of these age-related diseases initially affect different parts of the central nervous system, but are generally similar in terms of abnormal extracellular deposits, metabolic and oxidative stress, neuroinflammation, and microvascular abnormalities.(Sant'Anna, Navarro et al. 2016)
Another reason is that both diseases occur almost after a certain age and are mostly found in the elderly population, which further strengthened this similarity.(Giorgio, Zhang et al. 2018) ?n addition the leading cause of irreversible blindness (glaucoma) is progressive degeneration of the optic nerve and corresponding death of retinal ganglion cell.
There is strong evidence to suggest that the proliferation of neurodegenerative diseases and their specific ocular biomarkers play a crucial role in the development of retinal dysfunction or loss of vision function.(Reitz and Mayeux 2014)
References
Biscetti, L., et al. (2017). "Associations of Alzheimer’s disease with macular degeneration." Aging 27(24): 28.
Erkkinen, M. G., et al. (2018). "Clinical neurology and epidemiology of the major neurodegenerative diseases." Cold Spring Harbor perspectives in biology 10(4): a033118.
Fiorio, M., et al. (2006). "Selective impairment of hand mental rotation in patients with focal hand dystonia." Brain 129(1): 47-54.
Frost, S., et al. (2016). "Alzheimer’s disease and the early signs of age-related macular degeneration." Current Alzheimer Research 13(11): 1259-1266.
Giorgio, A., et al. (2018). "Diffuse brain damage in normal tension glaucoma." Human brain mapping 39(1): 532-541.
Guidoboni, G., et al. (2020). "Neurodegenerative disorders of the eye and of the brain: a perspective on their fluid-dynamical connections and the potential of mechanism-driven modeling." Frontiers in Neuroscience 14.
Heringa, S. M., et al. (2013). "Associations between retinal microvascular changes and dementia, cognitive functioning, and brain imaging abnormalities: a systematic review." Journal of Cerebral Blood Flow & Metabolism 33(7): 983-995.
Mancino, R., et al. (2018). "Glaucoma and Alzheimer disease: one age-related neurodegenerative disease of the brain." Current neuropharmacology 16(7): 971-977.
Reitz, C. and R. Mayeux (2014). "Alzheimer disease: epidemiology, diagnostic criteria, risk factors and biomarkers." Biochemical pharmacology 88(4): 640-651.
Sant'Anna, R., et al. (2016). "Amyloid properties of the leader peptide of variant B cystatin C: implications for Alzheimer and macular degeneration." FEBS letters 590(5): 644-654.
T Reed, B., et al. (2017). "Seeing early signs of Alzheimer's Disease through the lens of the eye." Current Alzheimer Research 14(1): 6-17.
