Submit a comment
Abstract
Protein misfolding and aggregation are thought to underlie the pathogenesis of many amyloid diseases, such as Alzheimer and Parkinson diseases, whereby a stepwise protein misfolding process begins with the conversion of soluble protein monomers to prefibrillar oligomers and progresses to the formation of insoluble amyloid fibrils. Drusen are extracellular deposits found in aging eyes and in eyes afflicted with age-related macular degeneration (AMD). Recent characterizations of drusen have revealed protein components that are shared with amyloid deposits. However, characteristic amyloid fibrils have thus far not been identified in drusen. In this study, we tested the hypothesis that nonfibrillar oligomers may be a common link in amyloid diseases. Oligomers consisting of distinct amyloidogenic proteins and peptides can be detected by a recently developed antibody that is thought to recognize a common structure. Notably, oligomers exhibit cellular toxicity, which suggests that they play a role in the pathogenesis of neurodegenerative diseases. Through use of the anti-oligomer antibody, we came to observe the presence of nonfibrillar, toxic oligomers in drusen. Conversely, no reactivity was observed in age-matched control eyes without drusen. These results suggest that amyloid oligomers may be involved in drusen biogenesis and that similar protein misfolding processes may occur in AMD and amyloid diseases.
Authors
Volker Luibl, Jose M. Isas, Rakez Kayed, Charles G. Glabe, Ralf Langen, Jeannie Chen
Guidelines
The Editorial Board will only consider comments that are deemed relevant and of interest to readers. The Journal will not post data that have not been subjected to peer review; or a comment that is essentially a reiteration of another comment.
- Comments appear on the Journal’s website and are linked from the original article’s web page.
- Authors are notified by email if their comments are posted.
- The Journal reserves the right to edit comments for length and clarity.
- No appeals will be considered.
- Comments are not indexed in PubMed.
Specific requirements
- Maximum length, 400 words
- Entered as plain text or HTML
- Author’s name and email address, to be posted with the comment
- Declaration of all potential conflicts of interest (even if these are not ultimately posted); see the Journal’s conflict-of-interest policy
- Comments may not include figures
Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)