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Global Translational Medicine Ocular changes in Alzheimer’s disease

protective factor whereas ε3 is considered the wild-type literature centers on the retina because it is derived
allele. Some early-onset cases, referred to as familial AD, from the diencephalon, rendering it comparable to
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account for 2% of cases and involve the inheritance of a the central nervous system (CNS). 4,17 The changes in
mutation that causes AD. These mutations are found in retinal cells of AD patients have been visualized using
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one of three genes, APP, presenilin 1, or presenilin 2, and immunohistochemical methods. The retina consists of
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result in the increased production of Aβ which is thought 10 layers: The inner limiting membrane, retinal nerve
to contribute to the initiation of AD pathology. Sporadic fiber layer (RNFL), ganglion cell layer (GCL), inner
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late-onset AD has no known cause, occurs after the age of plexiform layer, inner nuclear layer, outer plexiform layer
65 years, and accounts for approximately 95% of cases. (OPL), outer nuclear layer, external limiting membrane,
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Mild cognitive impairment (MCI) is a transitional state photoreceptor cell layer, and retinal pigment epithelium
before AD with symptoms of mild deficits in memory (Figure 2). Both the brain and retina contain high-
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and cognitive ability. Subjects with MCI may also have density neuronal cells and glial cells expressing proteins
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clinical symptoms from non-AD pathologies. However, involved in the amyloid cascade such as APOE and
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many cases of MCI convert to AD, specifically the amnestic γ-secretase. Furthermore, the brain and retina share
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type of MCI (aMCI). Research on the progression of similar vasculature. The retina can be used to assess
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AD typically compares controls with normal cognitive changes in the brain, and due to it being the only CNS
function to patients with MCI and/or AD. 13 tissue with no bone barrier, it is often referred to as the
2.3. Diagnosis “window” to the brain. 17,21
A definitive diagnosis of AD currently requires a post- 3.2. Imaging techniques
mortem evaluation of brain tissue to identify pathological The significance of the retina as the window to the brain is
signs such as Aβ plaques and NTs in the cerebral cortex. the possibility of using non-invasive imaging techniques
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For living patients, the diagnosis involves biomarkers to diagnose AD. For example, an amyloid probe curcumin
from cerebrospinal fluid (CSF), positron emission formulation was used to label Aβ in vivo and viewed using
tomography (PET), magnetic resonance imaging (MRI), a scanning laser ophthalmoscope (SLO). In contrast,
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or psychometric testing based on the diagnostic and the identification of structural changes avoids the step
statistical manual of mental disorder criteria. Although of labeling retinal Aβ. Optical coherence tomography
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CSF analysis provides quantitative information about (OCT) provides an image of the back of the eye, including
pathological molecules such as tau, and Aβ42, it is an the retina and choroid, and indicates the thickness of
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invasive procedure, and the results are not specific. For these structures. The resolution of an OCT is higher
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instance, elevated tau levels in CSF were also found in other than imaging methods such as an ultrasound or an MRI.
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neurodegenerative diseases such as Parkinson’s disease There are also new developments in OCT that improve its
and dementia with Lewy bodies. MRI detects changes imaging ability. For example, spectral domain (SD)-OCT
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in white and gray matter volume; however, the changes provides a higher resolution than the conventional time
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are not specific to AD, and an MRI cannot identify the domain OCT because it is 100 times faster and provides
small cerebral infarcts present in early AD. In addition, 4000 axial scans per second. 25,26 SD-OCT can also track the
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an MRI requires compliance from patients which can be eye during imaging, reducing noise and providing greater
difficult for patients with severe AD symptoms. PET, the detail. In addition, enhanced-depth imaging OCT is
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most specific diagnostic tool, uses imaging agents that used to image the choroid with greater clarity. There are
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bind to Aβ deposits, and small infarcts in the brain can also machines with an SLO attached to the OCT so the
be identified; however, it is expensive and carries harmful tests can be performed at the same time. In this case,
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side effects, limiting its value in clinical practice. 17,19 In the SLO can identify Aβ plaques in different quadrants
addition, if diagnosis occurs once extensive neuronal of the retina, and sections with high Aβ deposition can
damage has manifested, available AD treatment options
will prove ineffective. Therefore, developing a non- be isolated for focal scanning by OCT to determine the
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invasive screening test that will provide an early diagnosis retinal layer location. An OCT angiography maps the
is crucial. retinal microvasculature and provides information on
vessel density, size, and distribution. 28,29 Another option
3. The retina and AD to view retinal vascular is laser Doppler technology,
which examines blood column diameter and retinal blood
3.1. The retina flow rate. To summarize, there are several non-invasive
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There is substantial research focused on the changes imaging techniques to view the eye that can reflect AD
in the eye associated with AD. The vast amount of the pathology in the brain.
Volume 3 Issue 3 (2024) 3 doi: 10.36922/gtm.4094