Aβ/tau oligomer interplay at human synapses supports shifting therapeutic targets for Alzheimer's disease.

ABSTRACT:

Background

Alzheimer's disease (AD) is characterized by progressive cognitive decline due to accumulating synaptic insults by toxic oligomers of amyloid beta (AβO) and tau (TauO). There is growing consensus that preventing these oligomers from interacting with synapses might be an effective approach to treat AD. However, recent clinical trial failures suggest low effectiveness of targeting Aβ in late-stage AD. Researchers have redirected their attention toward TauO as the levels of this species increase later in disease pathogenesis. Here we show that AβO and TauO differentially target synapses and affect each other's binding dynamics.

Methods

Binding of labeled, pre-formed Aβ and tau oligomers onto synaptosomes isolated from the hippocampus and frontal cortex of mouse and p

SUBMITTER: Marcatti M 

PROVIDER: S-EPMC8979934 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature