Drusen deposits associated with aging and age-related macular degeneration contain nonfibrillar amyloid oligomers

Volker Luibl, Jose M. Isas, Rakez Kayed, Charles G. Glabe, Ralf Langen, Jeannie Chen

Research output: Contribution to journalArticle

133 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)378-385
Number of pages8
JournalJournal of Clinical Investigation
Volume116
Issue number2
DOIs
StatePublished - Feb 1 2006
Externally publishedYes

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Macular Degeneration
Amyloid
Proteins
Amyloidogenic Proteins
Poisons
Amyloid Plaques
Neurodegenerative Diseases
Parkinson Disease
Anti-Idiotypic Antibodies
Alzheimer Disease
Peptides
Antibodies

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Drusen deposits associated with aging and age-related macular degeneration contain nonfibrillar amyloid oligomers. / Luibl, Volker; Isas, Jose M.; Kayed, Rakez; Glabe, Charles G.; Langen, Ralf; Chen, Jeannie.

In: Journal of Clinical Investigation, Vol. 116, No. 2, 01.02.2006, p. 378-385.

Research output: Contribution to journalArticle

Luibl, Volker ; Isas, Jose M. ; Kayed, Rakez ; Glabe, Charles G. ; Langen, Ralf ; Chen, Jeannie. / Drusen deposits associated with aging and age-related macular degeneration contain nonfibrillar amyloid oligomers. In: Journal of Clinical Investigation. 2006 ; Vol. 116, No. 2. pp. 378-385.
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