Temporal profile of amyloid-β (Aβ) oligomerization in an in vivo model of Alzheimer disease -: A link between Aβ and tau pathology

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.