Temporal Profile of Amyloid- beta (A beta ) Oligomerization in an in Vivo Model of Alzheimer Disease: A LINK BETWEEN A beta AND TAU PATHOLOGY

• Published in: The Journal of biological chemistry 2006-01, Vol.281 (3), p.1599-1604
• Main Authors: Oddo, Salvatore, Caccamo, Antonella, Tran, Levina, Lambert, Mary P, Glabe, Charles G, Klein, William L, LaFerla, Frank M
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M507892200

Accumulation of amyloid- beta (A beta ) is one of the earliest molecular events in Alzheimer disease (AD), whereas tau pathology is thought to be a later downstream event. It is now well established that A beta exists as monomers, oligomers, and fibrils. To study the temporal profile of A beta oligomer formation in vivo and to determine their interaction with tau pathology, we used the 3xTg-AD mice, which develop a progressive accumulation of plaques and tangles and cognitive impairments. We show that SDS-resistant A beta oligomers accumulate in an age-dependent fashion, and we present evidence to show that oligomerization of A beta appears to first occur intraneuronally. Finally, we show that a single intrahippocampal injection of a specific oligomeric antibody is sufficient to clear A beta pathology, and more importantly, tau pathology. Therefore, A beta oligomers may play a role in the induction of tau pathology, making the interference of A beta oligomerization a valid therapeutic target.