This is an interesting paper suggesting that components of Drusen may contain Abeta deposits. If true, this may implicate Abeta deposition in macular degeneration. The confocal immunostaining in Fig. 2 of this paper is impressive. My concern is whether the antibodies are detecting Abeta or not. The anti-Abeta antibody 6E10 can also detect APP. The use of 4G8 should be specific for Abeta. What is concerning to me is that there is robust anti-Abeta positive immunostaining of cultured retinal pigment cells. This is unexpected as unless Abeta aggregates the signal of endogenous Abeta from immunostaining, even in cells with high expression of APP, is usually undetectable. It would have been interesting to see results using a few other anti-Abeta antibodies in this study. Some of the best for immunostaining are polyclonals. It would have also been useful to utilize Congo Red or thioflavine to see if any of the anti-Abeta immunoreactive structures were true amyloid. Finally, if Abeta is really building up, an Abeta ELISA of a piece of retina with a lot of Drusen vs. no Drusen...  Read more

This is an interesting paper suggesting that components of Drusen may contain Abeta deposits. If true, this may implicate Abeta deposition in macular degeneration. The confocal immunostaining in Fig. 2 of this paper is impressive. My concern is whether the antibodies are detecting Abeta or not. The anti-Abeta antibody 6E10 can also detect APP. The use of 4G8 should be specific for Abeta. What is concerning to me is that there is robust anti-Abeta positive immunostaining of cultured retinal pigment cells. This is unexpected as unless Abeta aggregates the signal of endogenous Abeta from immunostaining, even in cells with high expression of APP, is usually undetectable. It would have been interesting to see results using a few other anti-Abeta antibodies in this study. Some of the best for immunostaining are polyclonals. It would have also been useful to utilize Congo Red or thioflavine to see if any of the anti-Abeta immunoreactive structures were true amyloid. Finally, if Abeta is really building up, an Abeta ELISA of a piece of retina with a lot of Drusen vs. no Drusen should detect a big difference. This paper is very suggestive of an intersting phenomenon with Abeta but I think it is not entirely clear if Abeta is what is building up. I'm sure it will be sorted out soon.

View all comments by David Holtzman

Interesting localization of abeta at sites of macular degeneration. The abeta lies outside the retinal pigment epithelium, so I guess this is technically outside the nervous system (?) The authors argue that the abeta may activate local inflammatory response by analogy to AD amyloid plaques. This may be a bit of a stretch.

View all comments by Eddie Koo