There is a great unmet need for a simple, inexpensive and non-invasive test that could be applied on a large scale to screen for Alzheimer’s disease (AD).
Finding a biomarker for AD for clinical use has been a real challenge for the field of biomarkers in the central nervous system (CNS).
Biomarkers for Alzheimer’s
A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathological processes or pharmacologic responses to a therapeutic intervention.
The current way to definitively diagnose AD is through brain scans and tests of cerebrospinal fluid (CSF) that must be collected via lumbar puncture but these procedures are invasive and expensive.
These challenges created opportunities for biomarkers that can be measured in the simplest way and that are also less invasive and less expensive. The eye is easy to access, possesses clear optics and shares many vascular and neural similarities to the brain.
Inside the eye, the retina, which is a projection of the CNS and a ‘window to the brain’, represents a new potential biomarker for AD.
These connections between the brain and the retina has led researchers to suspect that neurodegenerative diseases may have a similar pathology in the optic nerve and in retinal ganglion cells (RGCs).
The development of modern imaging techniques have improved the visualisation of detailed structure and functions of the retina and allowed clinicians and researchers to arrive at potentially early diagnosis.
Detection of apoptotic retinal cells
At the 14th International Conference on Alzheimer’s disease and Parkinson’s disease (PD) in Lisbon, a team from UCL London presented the detection of apoptotic retinal cells (DARC) as a novel imaging technology for monitoring RGC apoptosis and which could potentially serve as a biomarker in neurodegenerative diseases.
DARC uses fluorescently labelled annexin V to identify apoptosis retinal cells and binds to actively apoptotic and sick cells to enable single imaging in the retina.
In early apoptosis, the cell membrane changes in structure and phosphatidylserine move from the inside to the outside of the cell with the fluorescent labelled Annexin V that binds to the exposed phosphatidylserine.
Furthermore, Individual apoptotic cells appear as white spots on the retina and experimental studies show DARC as an early marker of glaucoma.
A Phase I clinical trial using DARC in healthy subjects and those with glaucoma has been completed and the results showed that DARC counts significantly greater in patients who later showed increasing rates of disease progression.
A phase II clinical trials in glaucoma, age-related macular degeneration (AMD), AD (Down’s), and multiple sclerosis (MS- optic neuritis) has been recently completed and DARC is considered a promising new retinal biomarker/diagnostic comprising fluorescently labelled annexin V and a potential for early detection of neurodegeneration and prompt treatment response in many CNS indications, however, it needs clinical validation with multiple trials.
Development of imaging technologies for eye and brain disease could help in the diagnosis of early neurodegeneration, the assessment of disease progression, the response of treatment and importantly a significant clinical trial length reduction.