Alzheimer's disease and retinal neurodegeneration share a consistent stress response of the neurovascular unit.

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology

PubMedID: 23171816

Busch S, Wu L, Feng Y, Gretz N, Hoffmann S, Hammes HP. Alzheimer's disease and retinal neurodegeneration share a consistent stress response of the neurovascular unit. Cell Physiol Biochem. 2012;30(6):1436-43.
BACKGROUND
The pathogenesis of Alzheimer's disease (AD) is characterized by neuronal injury, activation of microglia and astrocytes, deposition of amyloid-ß and secondary vessel degeneration. In the polycystic kidney disease (PKD) rat model, we observed neuronal injury, microglial activation and vasoregression. We speculated that this neuroretinal degeneration shares important pathogenetic steps with AD. Therefore, we determined the activation of astrocytes and the accumulation of amyloid-ß in PKD retinae.

METHODS
Immunohistochemistry of PKD retinae for vimentin, carboxymethyllysin, beta-Amyloid 1-42, High-Mobility-Group- Protein B1 and amyloid protein precursor was performed.

RESULTS
Adjunct to astrocyte activation, accumulation of beta-Amyloid 1-42 and High-Mobility-Group-Protein B1 in astrocytes and around vessels of the superficial network was found in PKD retinae prior to the onset of vasoregression. Amyloid precursor protein was localized adjacent to the outer segment of photoreceptors in PKD and control rats. The parallel appearance of AD-related peptides indicates an alarmine based response to photoreceptor degeneration and secondary vasoregression.

CONCLUSION
The model has broad overlap with AD and may be suitable to study beneficial pharmacological concepts.