Selective detection of amyloid-β oligomers using an ELISA based on conformation-specific antibodies in a transgenic rat model of Alzheimer’s disease

Soluble amyloid-β oligomers (AβOs) are conformational species associated with early synaptic dysfunction and neuronal damage. Experimental models without detectable plaque accumulation allow investigation of their role in early amyloid pathology. However, their heterogeneity and low abundance make their specific detection in biological samples challenging, requiring sensitive and selective detection strategies. Hippocampal and cortical homogenates and cerebrospinal fluid (CSF) samples from 6-month-old male and female Tg+/− McGill-R-Thy1-APP rats and WT controls were analyzed using a sandwich ELISA based on AβO-specific antibodies. In this ELISA, a conventional mAb NU1 was used as a capture antibody and the recombinant M13 bacteriophage displaying the AβO-specific single-chain variable fragment (scFv) NUsc1 on its surface was used for detection. The results showed higher AβO levels in hippocampal and cortical homogenates from Tg animals compared to WT controls. AβO levels were also increased in CSF from Tg animals in relation to WT controls, with statistically significant differences in all three comparisons. This approach enabled the detection of AβOs in brain tissue and CSF at an early stage of amyloid pathology, supporting its use for the molecular characterization of experimental AD models and the study of early oligomeric species. These findings emphasize the significance of evaluating AβOs as potential biomarkers for the identification of early disease stages.