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-β (Aβ) 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 Aβ exists as monomers, oligomers, and fibrils. To study the temporal profile of Aβ 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 Aβ oligomers accumulate in an age-dependent fashion, and we present evidence to show that oligomerization of Aβ appears to first occur intraneuronally. Finally, we show that a single intrahippocampal injection of a specific oligomeric antibody is sufficient to clear Aβ pathology, and more importantly, tau pathology. Therefore, Aβ oligomers may play a role in the induction of tau pathology, making the interference of Aβ oligomerization a valid therapeutic target.