Conformational targeting of intracellular Aβ oligomers demonstrates their pathological oligomerization inside the endoplasmic reticulum.

Aβ oligomers (AβOs) are crucially involved in Alzheimer's Disease (AD). However, the lack of selective approaches for targeting these polymorphic Aβ assemblies represents a major hurdle in understanding their biosynthesis, traffic and actions in living cells. Here, we established a subcellularly localized conformational-selective interference (CSI) approach, based on the expression of a recombinant antibody fragment against AβOs in the endoplasmic reticulum (ER).

Characterization of mitochondrial dysfunction in the 7PA2 cell model of Alzheimer's disease.

The 7WD4 and 7PA2 cell lines, widely used as cellular models for Alzheimer's disease (AD), have been used to investigate the effects of amyloid-β protein precursor overexpression and amyloid-β (Aβ) oligomer accumulation on mitochondrial function. Under standard culture conditions, both cell lines, compared to Chinese hamster ovary (CHO) control cells, displayed an ~5% decrease of O2 respiration as sustained by endogenous substrates. Functional impairment of the respiratory chain was found distributed among the protein complexes, though more evident at the level of complex I and complex IV.