Putative retinal gliosis may serve as biomarker for preclinical Alzheimer’s disease
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Key takeaways:
- The surface area of putative retinal gliosis was greater in patients with preclinical Alzheimer’s disease compared with a control group.
- Putative retinal gliosis could be a biomarker for neuroinflammation.
Patients with preclinical Alzheimer’s disease had significantly greater putative retinal gliosis compared with controls, according to study results published in Investigative Ophthalmology & Visual Science.
These results suggest putative retinal gliosis may serve as a potential biomarker for Alzheimer's disease (AD)-related neuroinflammation, according to the researchers.
“The classical structural biomarker investigated in AD with respect to the neurosensory retina includes the retinal nerve fiber layer (RNFL) thickness at the macular and the peripapillary region,” Swetha Ravichandran, a student researcher at University of Alabama at Birmingham School of Optometry, and colleagues wrote. However, a “lack of consistency” in this measure necessitates a search for other evaluation methods, they added.
Because AD mouse models and postpartum biopsies of patients with AD have shown retinal glial activation comparable to central nervous system immunoreactivity, the researchers hypothesized that the surface area of putative retinal gliosis would be larger in patients with preclinical AD.
Thus, they performed a cross-sectional multisite study involving 76 participants (132 eyes), including 22 patients with preclinical AD (40 eyes; mean age, 69 years; range, 60-80 years) and 20 controls (32 eyes; mean age, 66 years; range, 58-82 years).
The researchers measured differences in the surface area of putative retinal gliosis in preclinical AD patients vs. controls using OCT en face imaging, and they also examined the association between this measurement compared with RNFL thickness at nine ETDRS map sectors.
According to results, the surface area of putative retinal gliosis was significantly greater in the preclinical AD group (0.97 ± 0.55 mm2; range, 0.134-2.39) compared with the control group (0.68 ± 0.4 mm2; range, 0.145- 1.36; P = .039).
There was no significant difference in RNFL thickness between groups at ETDRS sectors. However, the researchers discovered a trend towards thicker RNFL in the preclinical AD group, with the exception of the inner temporal region.
Next, researchers constructed receiver operating characteristic (ROC) models to determine whether the addition of RNFL thickness to putative retinal gliosis could better distinguish between preclinical AD and controls.
Results showed the ROC model based on surface area of putative retinal gliosis alone had an area under the curve of 0.63 (P = .05), which the researchers called “satisfactory.” In a multimodal ROC model that added inner inferior, inner superior and inner nasal RNFL thickness, the AUC improved to 0.68 (P = .004).
The researchers acknowledged several limitations to this study, mainly concerning its cross-sectional nature.
“These findings suggest the potential value of the surface area of putative retinal gliosis in early AD detection, monitoring disease progression and serving as surrogate endpoints for neuroinflammation in clinical trials related to AD,” Ravichandran and colleagues wrote.
Considering these results, future research should use a multimodal retinal structural approach for early AD detection and could examine a combined model of putative retinal gliosis and blood-based biomarkers, they added.
Perspective
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Being able to detect signs of AD in the preclinical stages is the goal of many scientists, as about one in nine individuals aged 65 years or older have Alzheimer’s dementia in the U.S. alone. And, of course, the overall number of Americans suffering from AD or other dementias is expected to grow, as Americans on average are living longer. Furthermore, some experts now believe that the brain changes can onset 20 years prior to the start of any AD symptoms.
That is why this article in particular is of great interest. We know that the retina is an extension of the brain, and the authors utilized this to their advantage to seek early diagnosis of AD. They found that putative gliosis is a potential biomarker, as it was greater in preclinical AD compared with similarly aged controls.
The findings not only have the potential for early AD detection, but they can offer insight into disease progression and serve very well during AD-related clinical trials.
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Ravichandran S, et al. Invest Ophthalmol Vis Sci. 2024;doi:https://doi.org/10.1167/iovs.65.5.5.
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