Abstract
Purpose: :
Patients with Alzheimer’s Disease (AD) have a true, primary optic neuropathy. Low-Density Lipoprotein Receptor-Related Protein (LRP) has been shown to be a possible mediator of the brain pathogenesis in AD . LRP is located in the endothelium of the blood brain barrier and is responsible for clearing Amyloid-Beta (Aß) out of the central nervous system. The purpose of this study is to quantify LRP in the optic nerves of AD patients in comparison to normals.
Methods: :
We looked at formalin-fixed, paraffin-embedded 5µm longitudinal sections of 24 retrobulbar optic nerves (5-7 mm from the globe) from 12 donors with AD. These were compared to 24 age-matched control optic nerves from 12 individuals with no AD. Comparisons were made after staining with an antibody directed against human LRP.
Results: :
Immunoreactivity for LRP in the vasculature of AD nerves was about one-tenth that seen in age-matched control nerves (average number of LRP immunolabeled plaques per 1.08mm2: AD 0.12; Controls 1.18 [p<0.002]).
Conclusions: :
The decreased presence of LRP in AD optic nerves suggests its involvement in the neurodegenerative process of this disease. Since LRP is responsible for the clearance of Aß out of the CNS, less LRP in the optic nerve may result in neurotoxic accumulation of Aß. This opens the way to new approaches to the therapy of AD including the upregulation of LRP to mitigate the accumulation of Aß.
Keywords: neuro-ophthalmology: optic nerve • receptors • pathology: human