- Despite growing numbers of people affected by Alzheimer’s disease, the mechanisms by which it affects the brain remain debated.
- This means that developing early diagnostic tests is challenging, which affects the development of clinical trials to test potential treatments.
- A recent study has suggested changes to the retina could shed some light on the progression of Alzheimer’s disease.
One of the challenges with treating Alzheimer’s disease is that symptoms often appear after the damage has already been done to the brain.
Many treatments being developed target the protein beta-amyloid, as Alzheimer’s disease is characterized by the buildup of plaques of this protein in the brain, affecting the neurons’ ability to signal. This leads to cognitive decline.
Finding ways to detect Alzheimer’s disease as it develops could help affected individuals access appropriate treatment earlier and limit the damage that causes cognitive decline.
Now, a study published in the journal
The researchers looked at 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 status of the brain.
The retina also has its own blood barrier, formed of tightly joined cells that prevent harmful substances from entering the retinal tissue.
The researchers’ main finding was of up to 70% disruption of the retinal blood barrier in people with Alzheimer’s disease and mild cognitive impairment compared to those with healthy cognition, meaning harmful substances could pass through the barrier and enter the retinal tissue.
Researchers looked at the proteins found in the retinas and discovered vascular beta-amyloid deposits in people with Alzheimer’s disease occurred mainly in the arterioles. This accumulation made the arterioles stiff, preventing them from clearing harmful substances from the retina.
It was unclear, however, whether beta-amyloid buildup caused the problem or whether damage to the arterioles resulted in the buildup.
For the first time, researchers discovered a link between a condition called cerebral amyloid angiopathy, a vascular disease in the brain characterized by the accumulation of amyloid proteins in small blood vessels, and disruption of the retinal blood barrier.
Previously it has only been possible to diagnose this condition post-mortem. Researchers suggested that with further research and improvements in imaging techniques, it may be possible to diagnose this in living patients.
While the findings were significant, they have not been reproduced in living patients, as all of the retinas investigated in the laboratory were from deceased donors.
The lack of early diagnostic tests for Alzheimer’s disease means that not only is it difficult to treat, but it is also difficult to design clinical trials around.
There are also controversies around the accelerated approval of two drugs in the past year: lecanemab and aducanumab.
While study results for aducanumab show a reduction in beta-amyloid buildup in the brain, it is not clear if the drug can slow cognitive decline. It has been suggested that providing the drug earlier in the progression of the disease could result in better outcomes, but the inability to identify these patients means they can’t be included in clinical trials.
Dr. Theodore Strange, associate chair of medicine at Staten Island University Hospital and a specialist in geriatrics told Medical News Today:
“This whole issue of tau protein and amyloid deposits are something that’s been explored in years, and we’re still trying to grapple with and get our hands around.”
However, as much as there is controversy around amyloid deposits and their link to Alzheimer’s, some experts consider these developments promising.
Dr. Thomas Hanscom ophthalmologist and retina specialist at Providence Saint John’s Health Center in Santa Monica, California told MNT “The current study adds to the evidence supporting the ‘amyloid theory’ of Alzheimer’s disease.”
Dr. Hanscom also described recent reports about the effectiveness of Donanemab as “exciting.”
“This drug seemed to slow the progress of Alzheimer’s disease, and this benefit was correlated with the elimination of amyloid from the brain. This clinical research will energize the quest for a reliable amyloid marker in the retina. Several companies are trying to develop such a test,” he said.
One 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 that few metabolites from the brain make it into the bloodstream. This makes it difficult to detect changes that are occurring in the brain.
“[Biomarkers] may help us in further treatment options, or causes or early detection especially if there [are] other diseases like diabetes, early diabetes, dementia, and the deposition of these plaque[s],” said Dr. Strange.
Dr. Tharick Pascoal, associate professor of psychiatry and neurology at the University of Pittsburgh, told MNT 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, though it is