Detection of retinal and blood Aβ oligomers with nanobodies

Introduction: Abnormal retinal changes are increasingly recognized as an early pathological change in Alzheimer’s disease (AD). Although amyloid beta oligomers (Aβo) have been shown to accumulate in the blood and retina of AD patients and animals, it is not known whether the early Aβo deposition precedes their accumulation in brain. Methods and results: Using nanobodies targeting Aβ1-40 and Aβ1-42 oligomers we were able to detect Aβ oligomers in the retina and blood but not in the brain of 3-month-old APP/PS1 mice. Furthermore, Aβ plaques were detected in the brain but not the retina of 3-month-old APP/PS1 mice. Conclusion: These results suggest that retinal accumulation of Aβo originates from peripheral blood and precedes cognitive decline and Aβo deposition in the brain. This provides a very strong basis to develop and implement an “eye test” for early detection of AD using nanobodies targeting retinal Aβ.