Introduction

Alzheimer’s disease (AD) is a progressive neurological disorder that affects 46 million people aged 60 and older globally. It is expected to increase to 131.5 million by 2050.⁴ Alzheimer’s is the sixth leading cause of death in the U.S., along with being the fifth leading cause of death in Americans aged 65 and older.¹⁰ AD is thought to start many years before noticeable symptoms occur. Only after some years do symptoms emerge that are noticeable to the individual, they appear as changes in the brain such as memory loss and language difficulty. AD is believed to have resulted from multiple factors rather than a single cause.¹⁰ Uncommon genetic changes, several genes that have increased the risk of AD, and a family history of having a parent or sibling with Alzheimer’s are more likely to develop the disease.¹⁰ There are two abnormalities that are known biomarkers of AD, the accumulation of proteins fragments beta-amyloid (Aβ plaques), and twisted strands of the protein tau (neurofibrillary tangles).⁸ In this article, the main focus is the Aβ plaques that build up outside of the neurons in the brain. These changes break down nerve cells leading to damage and death to brain tissue. The deposition of Aβ plaque is associated with cross-sectional synaptic network dysfunction, progressive brain atrophy, and cognitive decline.⁸ Current treatments for AD are pharmacological treatments but do not slow down or cure the damage and breakdown of neurons that progress in AD.⁹ Medication such as donepezil is currently being used by inhibiting acetylcholinesterase providing a temporary improvement in cognitive symptoms by increasing numbers of neurotransmitters (acetylcholine) within the brain, increased concentration leads to improvement in mental function with a slow progression of dementia.^6,9 While the medication is being used for temporary cognitive symptoms, there are behavioral and psychiatric symptoms that may be developed in the moderate to severe stages of AD. There is an importance in finding a less risky treatment and more effective for AD.⁹ Currently brain scans are being used to help detect signs and biomarkers of AD There have been studies that have discovered a potential noninvasive way of detecting AD early on through the retina by ocular imaging, a more accessible entry point for imaging than the brain.⁸ Imaging the retina will allow for identifying changing blood vessels that can provide early signs of Alzheimer’s before there is a decline in cognitive function.³ Being able to use visual imaging to identify AD would be faster, less expensive, and hopefully provide an early diagnosis before the onset of AD to first find a treatment to slow down the progression of AD, reverse the progression of AD, or even cure AD before it starts to become severe and then use the treatment when early signs of AD start showing up through ocular imaging.¹⁰ The purpose of this review is to find new advancements in technology that make it faster and easier to detect the onset of neurodegenerative diseases to be able to find a way to treat the disease before they become severe.

Locating amyloid β-protein (Aβ) deposits in blood vessels

Alzheimer’s disease has an accumulation of Aβ plaques that build up outside the brain’s neurons. Aβ accumulation starts many years before you can diagnose AD in individuals by the brain.⁸ These changes break down nerve cells leading to damage and death of tissue in the hippocampus region of the brain. Aβ consists of a 36-43 amino acid peptide.³ A family of Aβ contains amyloidogenic cleavage from amyloid precursor protein (APP) expresses neuronal and non-neuronal cell types in the body.⁸ The abnormal accumulation of Aβ in the brain correlates with pathogenic protein aggregation, synaptic dysfunction, and neurotoxicity.⁸ The retina has similarities with the brain, such as being connected by blood vessels. By the connection, it could potentially predict the accumulated Aβ in the brain just by retinal imaging.⁷ In a study about the retina of individuals, there has been a discovery of Aβ being associated with the cataract of individuals with AD.⁸ By having access to retinal imaging, amyloid deposits would be of an advantage compared to the brain, where you have easier access to the eye through in vivo imagining.¹

The technology used to detect amyloid β-protein (Aβ) deposits

Ocular imaging is currently being studied as a potential noninvasive way to detect AD through retinal imaging. Using laser ophthalmoscopy and amyloid-binding fluorophore curcumin to evaluate retinal amyloid in three different sections of the retina, there is a chance of detecting AD diseases early on before AD takes place by retinal scan based on a significant association in retinal amyloid in the proximal, mid periphery (PMP) topographical region that seemed to be paired significantly with hippocampal volume and low cognitive scores.²  Curcumin has a chemical structure that binds to beta-pleated sheets in Aβ that bind with high affinity, enhancing the retinal fluorescence imaging.² In both males and females, the left eye was chosen for comparative and correlation analysis. The retinas showed the presence of Aβ, phosphorylated tau, neurodegeneration, and other AD pathologies found in AD individuals’ brains.² Another study was conducted to see if there was a difference in retinal imaging between males and females. The study used optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) on neuronal layers, retinal microvasculature, and choroidal structure.⁴ The optical coherence was used to identify differences in neuronal loss in the brain parenchyma and retina differences in males and females.⁴ They found no difference in retinal microvasculature, retinal structure, or choroidal structure between males and females that had signs of AD.⁴ Women had a larger foveal avascular zone (FAZ) area compared to men and a thinner central subfield thickness (CST) present in retinal microvasculature.⁴ Despite the different imaging techniques used for identifying Aβ in the retina, there is a correlation between Aβ and other signs of AD being found within the retina as the symptoms are usually observed within the brain.

Conclusion

Alzheimer’s disease is a progressive neurodegenerative. While there are around 46 million people are affected it is only expected to double in the near future.⁴  There is no approved retinal imagining diagnosis of early Alzheimer’s disease, but as retinal imaging is being studied as a potential noninvasive method in investigating AD and other neurodegenerative changes, it seems that there may be hope in the near future. Having access to retinal imaging amyloid deposits would be an advantage compared to the brain, where you have easier access to the eye through in vivo imagining.¹ More studies are needed to investigate in area of interest for future studies would be PMP and posterior (PP) in the supertemporal area of ocular imaging to diagnose Alzheimer’s early on because these areas of blood vessels are what relates most to the hippocampal area of the brain. It would help by developing a treatment that can slow down or even stop the progression of dementia by giving a better chance of benefiting from the treatment allowing for more minor risk factors to take place.

[+] References

[+] Other Work By Aisha El-Hoot