- Despite a growing number of people affected by Alzheimer’s disease, the mechanisms by which it affects the brain remain debated.
- This means that the development of early diagnostic tests is difficult, which affects the development of clinical trials to test potential treatments.
- A recent study suggested that changes in the retina may shed light on the progression of Alzheimer’s disease.
One of the challenges of treating Alzheimer’s disease is that symptoms often appear after damage has already been done to the brain.
Many treatments in development target the beta-amyloid protein, because Alzheimer’s disease is characterized by the accumulation of plaques of this protein in the brain, affecting the signaling capacity of neurons. This leads to cognitive decline.
Finding ways to detect Alzheimer’s disease as it develops could help those affected access appropriate treatment earlier and limit the damage that causes cognitive decline.
Now, a study published in the journal Alzheimer’s and dementiashowed that changes in the retina of people with Alzheimer’s disease mimic many of those in the brain.
The researchers examined the retinas of 24 deceased human donors with Alzheimer’s disease, 10 donors with mild cognitive impairment and 27 with healthy cognition.
The retina is the part of the eye that converts light into nerve signals that allow us to see. During embryonic development, it develops as an extension of the brain and as such can give us unique insight into the state of the brain.
The retina also has its own blood barrier, formed of tightly bound cells that prevent harmful substances from entering the retinal tissue.
The researchers’ main finding was to disrupt the retinal blood barrier by up to 70% in people with Alzheimer’s disease and mild cognitive impairment compared to those with healthy cognition, which means that harmful substances could cross the barrier and penetrate the retinal tissue.
The researchers examined the proteins found in the retinas and found that vascular deposits of beta-amyloid in people with Alzheimer’s disease occur primarily in the arterioles. This buildup made the arterioles stiff, preventing them from clearing harmful substances from the retina.
It was unclear, however, whether beta-amyloid buildup was causing the problem or if arteriolar damage was causing the buildup.
For the first time, researchers have discovered a link between a condition called cerebral amyloid angiopathy, a vascular disease of the brain characterized by the accumulation of amyloid proteins in small blood vessels, and disruption of the blood-retinal barrier.
Previously, it was only possible to diagnose this condition post-mortem. The researchers suggested that with further research and improvements in imaging techniques, it may be possible to diagnose this in living patients.
Although the results were significant, they have not been replicated in living patients, as all of the retinas studied in the laboratory were from deceased donors.
The lack of early diagnostic tests for Alzheimer’s disease not only means that it is difficult to treat, but it is also difficult to design clinical trials.
There are also controversies surrounding the accelerated approval of two drugs over the past year: lecanemab and aducanumab.
Although the results of the aducanumab study show a reduction in beta-amyloid accumulation in the brain, it is unclear whether the drug can slow cognitive decline. It has been suggested that providing the drug earlier in disease progression could lead to better outcomes, but the inability to identify these patients means they cannot be included in clinical trials.
Dr Theodore Strangeassociate director of medicine at Staten Island University Hospital and specialist in geriatrics said Medical News Today:
“This whole issue of tau and amyloid deposits is something that’s been explored for years, and we’re still trying to come to grips with it and get our hands on it.”
However, although there is controversy surrounding amyloid deposits and their link to Alzheimer’s disease, some experts see these developments as promising.
Dr. Thomas Hanscom ophthalmologist and retina specialist at Providence Saint John’s Health Center in Santa Monica, Calif., said DTM “The current study adds to the evidence supporting the ‘amyloid theory’ of Alzheimer’s disease.”
Dr. Hanscom also described recent reports of donanemab’s effectiveness as “exciting.”
“This drug appeared to slow the progression of Alzheimer’s disease, and this benefit was correlated with the removal of amyloid from the brain. This clinical research will boost the search for a reliable amyloid marker in the retina. Several companies are trying to develop such a test,” he said.
A problem associated with developing a blood test for Alzheimer’s disease is that the disease primarily affects the brain, and the blood-brain barrier means few metabolites from the brain make it into the bloodstream. This makes it difficult to detect changes occurring in the brain.
“(Biomarkers) can help us with other treatment options, or causes or early detection, especially if there are other diseases like diabetes, early onset diabetes, dementia and the deposition of these plaques “Dr. Strange said.
Dr. Tharick Pascoalassociate professor of psychiatry and neurology at the University of Pittsburgh, said DTM that observing changes in the brain can be invasive and expensive.
“You have biomarkers that involve lumbar punctures that measure this amyloid pathology in the cerebrospinal fluid of patients and PET scans. These exams are expensive or difficult to do,” he said.
However, vascular changes are common in people with Alzheimer’s disease, although it is not clear whether it is caused by Alzheimer’s disease or whether it is the prelude to it.