Dataset Information

Retinal Pathological Features and Proteome Signatures of Alzheimer’s Disease

ABSTRACT: Alzheimer’s disease (AD) pathologies were discovered in the easily accessible neurosensory retina. Yet, their specific nature, topographical distribution, and relationship with disease status remain undefined. Here, we histologically determined burden and spatial distribution of amyloid β-protein (Aβ42 ), intraneuronal scFvA13 + -Aβ species, macro- and microgliosis, and atrophy in superior- and inferiortemporal retinas of human donors with mild cognitive impairment (MCI) or AD versus normal cognition. AD and MCI patients had enhanced retinopathy, predominantly affecting inner layers and peripheral subregions, which quantitatively correlated with severity of cerebral amyloid, tau, and neurodegeneration, and cognitive scores. In advanced clinical stages AD retinopathy further affected central outer segments. Increased retinal macrogliosis and Aβ-phagocytosing microglia were detected in MCI and AD patients. Further, distinct proteome profiles of AD retinas were identified, displaying greater overlap with the temporal cortices than with hippocampi or cerebella. AD retinas exhibited upregulated inflammatory and neurodegenerative processes and downregulated oxidative-phosphorylation/mitochondrial, and photoreceptor-related pathways. This study identifies and maps AD retinopathy, demonstrating the quantitative relationship with brain pathology and cognition.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain, Retina

DISEASE(S): Alzheimer's Disease

SUBMITTER: Mehdi Mirzaei

LAB HEAD: Maya Koronyo

PROVIDER: PXD040225 | Pride | 2025-10-22

REPOSITORIES: Pride

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			Action	DRS
	191218_P90062_Human_Retina_HFX_TMT1_HpH_1.raw	Raw
	191218_P90062_Human_Retina_HFX_TMT1_HpH_10.raw	Raw
	191218_P90062_Human_Retina_HFX_TMT1_HpH_11.raw	Raw
	191218_P90062_Human_Retina_HFX_TMT1_HpH_12.raw	Raw
	191218_P90062_Human_Retina_HFX_TMT1_HpH_13.raw	Raw

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Retinal pathological features and proteome signatures of Alzheimer's disease.

Koronyo Yosef Y Rentsendorj Altan A Mirzaei Nazanin N Regis Giovanna C GC Sheyn Julia J Shi Haoshen H Barron Ernesto E Cook-Wiens Galen G Rodriguez Anthony R AR Medeiros Rodrigo R Paulo Joao A JA Gupta Veer B VB Kramerov Andrei A AA Ljubimov Alexander V AV Van Eyk Jennifer E JE Graham Stuart L SL Gupta Vivek K VK Ringman John M JM Hinton David R DR Miller Carol A CA Black Keith L KL Cattaneo Antonino A Meli Giovanni G Mirzaei Mehdi M Fuchs Dieu-Trang DT Koronyo-Hamaoui Maya M

Acta neuropathologica 20230211 4

Alzheimer's disease (AD) pathologies were discovered in the accessible neurosensory retina. However, their exact nature and topographical distribution, particularly in the early stages of functional impairment, and how they relate to disease progression in the brain remain largely unknown. To better understand the pathological features of AD in the retina, we conducted an extensive histopathological and biochemical investigation of postmortem retina and brain tissues from 86 human donors. Quanti ...[more]

PMID: 36773106

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