Expression Of BACE-1in Retina And Brain In APP/PS-1Transgenic Mouse

Alzheimer’s disease (AD) is a kind of irreversibale neurodegenerative diseases. Older population used to be attacked by this disease. Those afflicted with Alzheimer’s suffer from memory loss, impaired decision-making, and diminished language and movement skills. It can not be halted or reversed after diagnosis. Nowadays, there is no efficient or reliable index for early diagnosis of this disease. So, it is important to find out indicator for early diagnosis. The neurotoxic of the aggregative polymerization of A(3contributes to this disease.(3-site APP cleaving enzyme1(BACE-1) participated in Aβ formation, as an important indicator in pathology of AD. The retina as an extension of the brain is portrayed an appealing target for a significant research of AD. So, in order to provide the evidences to find early diagnostic index, it was important to determine the expression of BACE-1in retina and brain. APP/PS-1transgenic mice (TG mice) with the C57/BL6genetic background were divided into different groups (3,6and8months), C57/BL6wild type mice (WT mice) of the same age were used as the control. Morris water maze test, nissl’s staining and immunohistochemistry staining were used in this experiment. The results are shown below.1) During4-day Morris water maze training, we found that the escape latent period prolonged at6and8months in TG groups on day3and day4as compared with the3months in TG mice, but not in WT mice. Compared with the WT mice of the same age, the escape latent period lengthened in TG mice at6months on day3and day4, the same trends emerged in TG mice at8months on day2, day3and day4.We found that TG mice showed a low preference for the former platform-containing quadrant at6and8months as compared with the3months, but not in WT groups. The results suggest that TG mice showed significantly worse memory ability at6months.2) The immunohistochemistry results showed that BACE-1 expression was prominent in hippocampus. BACE-1plaques were clearly expressed in entorhinal cortex, hippocampus and forehead cortex at6months and strengthened at8months in TG mice brain, but they were not detectable in3months TG mice and WT mice.In WT mice retinas, expression of BACE-1was barely at3months, the intensity was weak in the ganglion cell layer, inner and outer plexiform layer at6and8months. In TG mice retina, BACE-1expression was stable in ganglion cell layer and faint in inner plexiform layer at3months, while was increased in the ganglion cell layer, inner plexiform layer and was stable expressed in outer plexiform layer at6and8months.3) After the nissl’s staining, no significant decrease of positive cells in ganglion cell layer was observed between the TG mice and WT mice.The results indicated that the expression of BACE-1in retina was prior to behavior changes and BACE-1alteration in brain. It provided the experimental evidences to seek for the early diagnostic indicator of Alzheimer’s disease.