ALZHEIMER’S RETINOPATHY: EARLY PERICYTE LOSS, VASCULAR AMYLOIDOSIS, PDGFRΒ DEFICIENCY, AND BRB BREAKDOWN CAN PREDICT COGNITIVE STATUS
- Maya Koronyo-Hamaoui, United States of America
Abstract
Aims
Interrogation of Alzheimer’s disease (AD) in the neurosensory retina, a CNS organ easily accessible for noninvasive imaging, is undertaken to improve early AD detection and monitoring. Here, we sought to identify and characterize retinal vascular molecular and cellular parameters that appear to play a prominent role in early brain AD-related pathogenesis and further associate with cognitive decline.
Methods
We comprehensively evaluated microvascular degeneration, pericyte integrity, platelet-derived growth factor receptor-β (PDGFRβ) expression, vascular amyloidosis, and molecular pathways related to the blood-retinal barrier (BRB) in postmortem retinas from mild cognitively impaired (MCI) and AD patients compared with age- and sex-matched cognitively normal controls (n=62 subjects). Retinal cross-sections and isolated vascular network from predefined retinal regions were analyzed. Retinal vascular parameters were correlated with brain pathology.
Results
We revealed early, progressive and substantial decreases in vascular PDGFRβ expression and pericyte numbers in the retina of MCI and AD patients that were linked to retinal vascular Aβ40 and Aβ42 burden. Decreased vascular low-density lipoprotein receptor-related protein 1 (LRP1) and an early increase in pericyte apoptosis were also detected in MCI and AD retinas. Mapping of PDGFRβ and Aβ40 levels in pre-defined retinal subregions indicated that certain geometrical and cellular layers are more susceptible to AD pathology. Further, significant correlations were found between retinal vascular abnormalities and cerebral amyloid angiopathy and cognitive status.
Conclusions
The identification of early vascular PDGFRβ deficiency, pericyte loss, and tight-junction disruptions along with vascular amyloidosis in the AD retina implies a compromised BRB integrity and provides new targets for AD diagnosis and therapy.