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LUIS F FERNANDO HERNANDEZ, Abigail Torres, Monserrat Perez, Elisa Gorostieta, Miriam Catorce, Gonzalo Acero, Gohar Gevorkian, Ruben Zamora, Hugo Quiroz; Beta amyloid peptides accumulation induces the over expression of TSPO translocator in optic nerve, visual cortex and in the retina in Alzheimer s disease and aging model. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1742.
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Our current research is being performed to probe if βA42 peptide and amyloid N-truncated species (AβN3(pE), AβN11(pE)) are involved in vission loss in AD and if these peptides are involved in the overexpression of the prtoein translocator TSPO in the same tissues.Murine transgenic models of Alzheimer’s disease (Tg-AD) have been used to analyze the presence of β-amyloid precursor protein (β-APP), βA 1-42 (ßA42) , and N-truncated peptides like AβN3(pE), and AβN11(pE) deposition in the brain. These peptides are cytotoxic and the principal markers in AD. Recently, the ßA42 has been involved in vision loss. The presence of multiple ßA42 reservoirs in the the retina environment, induces pathologies that leads to deficient vision and blindness. However, for our knowledge, there is not any evidence of AβN3(pE), and AβN11(pE) accumulation in Visual Cortex (VC), in retina and optic nerve of 3xTg-AD mice as well as adult Wild-Type mice. Both peptides, are more toxic than ßA42 and they are correlated with neuroinflammatory processes in AD.
We have studied the deposition of, βA-42, AβN3-42(pE), and AβN11-42(pE) and overexpression of TSPO in retina and visual cortex in a 4 months old (4M) and 16 months old (16M) of 3xTg-AD mice and 4M and 16 months old aged symptomatic mice (C57BL/6 WT). Immunohistochemistry: Brain sections (30 uM) and enucleated eyes from both animal models were processed for double immunofluorescence (IF) and analyzed against the following: βA42, AβN3-42(pE), and AβN11-42(pE), pTau, GFAP and TSPO. Western blot: WB for each different βA peptide and for TSPO were performed in protein extracts from isolated retinas and visual cortex from both models
The results show the significant deposition of βA42 and AβN3-42(pE) peptides, p-TAU, and GFAP and TSPO overexpression in retina in VC of WT mice at 24 months old principally and 3xTg-AD. In these mice we have not detected AβN11(pE). These results could be related with the activation of inflammation mechanisms and visual loss in AD and aging.
For our knowledge, this is the first time that the AβN3(pE) peptide presence in the retina is reported, and this accumulation correlates with the overexpression of TSPO in retina and optic nerve. however, the pathological relevance of this remains to be elucidated.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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