- One way scientists think Alzheimer’s disease may be detected early is through eye Health.
- Specifically, scientists have been looking into the retina and its blood vessels in hopes that they could help identify changes that are also occurring in the brain.
- Results of a recent mouse study suggest distinct vascular changes in the eyes and brain occur at the same time, and that closer eye examination could ultimately help doctors detect Alzheimer’s and related dementias sooner.
Recent research in mice suggests distinct similarities between brain and eye blood vessel changes that happen with aging which could help with identifying Alzheimer’s disease and related dementias earlier.
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The results identified that eye vascular changes aligned with the brain vascular changes occurring in these mice. The researchers also observed certain protein changes relevant to Alzheimer’s disease in the mice’s brains and retinas.
This research builds on the idea that looking at the retina, a part of the eye, could be highly useful in detecting Alzheimer’s disease and related dementias. The authors note that problems with the cerebrovascular system are possibly some of the first noticeable changes that happen before someone develops mild cognitive impairment. They wanted to see if looking at the blood vessels of the retina could predict how well the blood vessels in the brain were functioning.
The research involved mice with a distinct variant in a gene. This variant has been linked to vascular dementia, Alzheimer’s disease, and some eye problems. Previous research by the same research group had already shown changes that occur in these mice, such as certain cerebrovascular deficits like those in Alzheimer’s disease and related dementia.
The mice in the current study with the variant belonged to one of three genotypes. When looking at a specific part of the retina, researchers did not see image abnormalities when the mice with the variant were six months old.
There wasn’t a major difference between the mice for a test measuring fluorescence intensity, which tends to increase with age. However, they did see a decrease in this area with age for some of the genotypes, with some differences between male and female mice and genotypes.
One change they did notice at 12 months in one of the groups of female mice was a decrease in the density of the retina’s blood vessels. The researchers suggest that this particular genotype has a bigger impact with increased age and among female mice.
Twelve-month-old female mice in this group also had changes that suggest the retina’s large blood vessel network was simplified. The researchers explain that their previous research showed a decrease in specific brain blood vessel density in mice with the genetic variant, particularly in the female mice.
They also observed other blood vessel changes in some of the mice. For example, they found an increase in twisted blood vessels for some mice, particularly for some of the twelve-month-old female mice. They also observed narrowing of the arteries and enlargement of the veins among all the mice with the genetic variant.
Among mice with the variant, researchers found that there wasn’t baseline changes in retinal thickness, indicating there was no nerve loss. This and other tests indicate that the variant by itself isn’t “inducing glaucoma-relevant phenotypes.”
Further tests revealed that the gene where this variant can be present is expressed quite a bit in the brain and retina. They identified certain proteins that were shared by the retina and the brain. When looking at proteins in the brains and retinas, researchers found that the sex and the genotype with the variant both contributed to protein differences in the brain. In the retina, the genotype appears to impact protein differences more than sex.
The authors note that these differentially expressed proteins are relevant to Alzheimer’s disease and further suggest that the involved genetic variant changes “pathways involving metabolism and cell survival similarly in both tissues.”
Overall, the results build on the previous research that mice with this genetic variant experience certain vascular changes in the brain, and that looking at the blood vessels in the retina could help with Alzheimer’s disease and related dementias being diagnosed early.
Maya Koronyo-Hamaoui, PhD, professor in the departments of Neurosurgery, Neurology, and Biomedical Sciences, at Cedars-Sinai Medical Center, LA, CA, who was not involved in the study, noted the following about the study to Medical News Today:
“This is a thoughtfully executed mouse study that strengthens the ‘ eye-brain’ axis for neurodegeneration. Using the MTHFR677C>T mouse model—relevant to human cerebrovascular risk—the authors show retinal microvascular abnormalities that mirror cerebrovascular phenotypes and report brain–retina overlap in differentially expressed, [Alzheimer’s disease]-relevant proteins.”
“Together, the data argue that the retina can report on disease-linked vascular biology in the brain, and that quantitative retinal imaging might serve as a minimally invasive readout of risk. As with any preclinical work, translation will require careful human validation, but the mechanistic signal and biomarker rationale are sound,” she explained.
Since this study was done in mice, it means that a lot more research is needed before we can really see application in people. Researchers suggest that since decreased retinal vessel density only happened in mice that were one year old, this test might not be an ideal one, since this happened earlier in the brain.
This study focused on vascular-related changes, so more information on how this relates to Alzheimer’s disease and related dementias will be valuable as well.
Daniel Romaus-Sanjurjo, PhD, Postdoctoral MSCA Fellow in the NeuroAging Group at the Health Research Institute of Santiago de Compostela (IDIS), Spain, who was also not involved in the study, noted the following limitations of the study:
“This study lacks ADRD [Alzheimer’s disease and related dementia]-related behavioral analysis (so we don’t really know if those mice had ADRD-like symptoms, which is critical to link the observed changes in eyes with dementia-like disease); and the fact that alterations in the MTHFR gene are also related to other diseases (including some affecting eye’s function) is another weakness, because authors couldn’t demonstrate that this mutant only shows vascular alterations affecting cognitive state of the animal.”
The authors note that examining the retinal vascular system is likely most helpful for a dementia subtype: “vascular contributions to cognitive impairment and dementia. (VCID).”
More research into the differentially expressed proteins may be useful. More research into the genotype’s true involvement will also be important, as well as more data on how the brain and retina vascular changes line up.
This research indicates the need to explore a lot more in this area.
“This is a preclinical study assessing the use of the Mthfr677C>T mice as a potential model for ADRD, especially the VCID (the one related to vascular changes). It is a characterization of the animal model focusing on the eye/retina to study vascular changes associated with the mutation. However, the vascular changes observed in this study can be related to other diseases (e.g. stroke) so this study should be taken carefully yet,” Sanjurjo noted.
However, it does also point to the immense usefulness of examining the eye for other changes that are occurring in the body. It suggests that in the future, eye exams could potentially help with the early detection of Alzheimer’s disease in some cases.
“The use of the retina as a source of biomarkers to detect Alzheimer’s/dementias earlier is an interesting and emerging field. Eyes have easy accessibility in the clinic through noninvasive methods that make them a good area to find new biomarkers in dementia.”
— Daniel Romaus-Sanjurjo, PhD
“However, it is not fully clear yet if ocular changes occur before or after brain changes, and what types of changes can be associated with dementia exclusively, as some ocular events related to AD are also shared by other ocular neurodegenerative pathologies, such as age-related macular degeneration (AMD) or glaucoma. Therefore, clarifying these aspects is mandatory to find compelling data regarding the use of eyes/retinas as biomarkers for ADRD,” added Sanjurjo.
