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New research · Ophthalmology
Acta neuropathologica · 5d
Cohort studyActa neuropathologica · 2026

Retinal proteome changes mirror brain pathology and reveal synaptic and cytoskeletal dysfunction in Alzheimer's disease.

Jessica Santiago, Dovilė Pocevičiūtė, Teo Sällberg … Malin Wennström
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OphthalmologyCohort study

64 proteins showed the same Alzheimer's-related changes in retina and brain

Retinal proteome changes mirror brain pathology and reveal synaptic and cytoskeletal dysfunction in Alzheimer's disease.

Jessica Santiago … Malin Wennström
Acta neuropathologica · 2026
Background

Visual dysfunction is increasingly recognized as an important feature of Alzheimer's disease, and substantial retinal changes have been documented across multiple studies.

Methods

Here, we performed comprehensive mass spectrometry-based proteomics on paired retinal and hippocampal tissue from the same postmortem donors (8 AD, 8 non-demented controls) to identify disease-associated molecular signatures and assess their overlap between these tissues.

n = 8 AD, 8 non-demented controls
64
Results
64
these proteins changed the same way in eyes and brain
n = 8 AD, 8 non-demented controls
More results

Using a sequential dual-extraction protocol, we identified 372 differentially abundant retinal proteins in AD, including established APP-processing regulators (SORL1, BACE1) and synaptic proteins.

Retinal proteomes clearly separated AD from controls in principal component analysis, indicating robust AD-related molecular differences in the retina.

More results

Several retinal proteins also correlated with neuropathological disease stage.

Cell-type mapping using single-cell retinal reference data indicated that most proteomic changes were broadly distributed across cell types, though some proteins showed enrichment in specific populations, such as SORL1 in microglia and EYS in photoreceptors.

“
Conclusion

Their similarities with brain pathology further support the retina as a promising window for assessing cerebral disease.

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