Novel Aß peptide immunogens modulate plaque pathology and inflammation in a murine model of Alzheimer's disease

Jun Zhou, Maria I. Fonseca, Rakez Kayed, Irma Hernandez, Scott D. Webster, Ozkan Yazan, David H. Cribbs, Charles G. Glabe, Andrea J. Tenner

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Background: Alzheimer's disease, a common dementia of the elder, is characterized by accumulation of protein amyloid deposits in the brain. Immunization to prevent this accumulation has been proposed as a therapeutic possibility, although adverse inflammatory reactions in human trials indicate the need for novel vaccination strategies. Method: Here vaccination with novel amyloid peptide immunogens was assessed in a transgenic mouse model displaying age-related accumulation of fibrillar plaques. Results: Immunization with any conformation of the amyloid peptide initiated at 12 months of age (at which time fibrillar amyloid has just begun to accumulate) showed significant decrease in total and fibrillar amyloid deposits and in glial reactivity relative to control transgenic animals. In contrast, there was no significant decrease in amyloid deposition or glial activation in mice in which vaccination was initiated at 16 months of age, despite the presence of similar levels anti-Aβ antibodies in young and old animals vaccinated with a given immunogen. Interestingly, immunization with an oligomeric conformation of Aβ was equally as effective as other amyloid peptides at reducing plaque accumulation. However, the antibodies generated by immunization with the oligomeric conformation of Aβ have more limited epitope reactivity than those generated by fAβ, and the microglial response was significantly less robust. Conclusions: These results suggest that a more specific immunogen such as oligomeric Aβ can be designed that achieves the goal of depleting amyloid while reducing potential detrimental inflammatory reactions. In addition, the data show that active immunization of older Tg2576 mice with any amyloid conformation is not as efficient at reducing amyloid accumulation and related pathology as immunization of younger mice, and that serum anti-amyloid antibody levels are not quantitatively related to reduced amyloid-associated pathology.

Original languageEnglish (US)
Article number28
JournalJournal of Neuroinflammation
Volume2
DOIs
StatePublished - Dec 7 2005
Externally publishedYes

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Amyloid
Alzheimer Disease
Pathology
Inflammation
Peptides
Immunization
Vaccination
Amyloid Plaques
Neuroglia
Anti-Idiotypic Antibodies
Genetically Modified Animals
Transgenic Mice
Dementia
Epitopes
Antibodies
Brain
Serum

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Novel Aß peptide immunogens modulate plaque pathology and inflammation in a murine model of Alzheimer's disease. / Zhou, Jun; Fonseca, Maria I.; Kayed, Rakez; Hernandez, Irma; Webster, Scott D.; Yazan, Ozkan; Cribbs, David H.; Glabe, Charles G.; Tenner, Andrea J.

In: Journal of Neuroinflammation, Vol. 2, 28, 07.12.2005.

Research output: Contribution to journalArticle

Zhou, Jun ; Fonseca, Maria I. ; Kayed, Rakez ; Hernandez, Irma ; Webster, Scott D. ; Yazan, Ozkan ; Cribbs, David H. ; Glabe, Charles G. ; Tenner, Andrea J. / Novel Aß peptide immunogens modulate plaque pathology and inflammation in a murine model of Alzheimer's disease. In: Journal of Neuroinflammation. 2005 ; Vol. 2.
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