Detection of retinal and blood Aβ oligomers with nanobodies

Umma Habiba; Joseph Descallar; Fabian Kreilaus; Utpal K Adhikari; Sachin Kumar; John W Morley; Bang V Bui; Maya Koronyo-Hamaoui; Mourad Tayebi

doi:10.1002/dad2.12193

Detection of retinal and blood Aβ oligomers with nanobodies

Alzheimers Dement (Amst). 2021 May 6;13(1):e12193. doi: 10.1002/dad2.12193. eCollection 2021.

Authors

Umma Habiba¹, Joseph Descallar^{2

3}, Fabian Kreilaus¹, Utpal K Adhikari¹, Sachin Kumar¹, John W Morley¹, Bang V Bui⁴, Maya Koronyo-Hamaoui⁵, Mourad Tayebi¹

Affiliations

¹ School of Medicine Western Sydney University Campbelltown New South Wales Australia.
² South Western Sydney Clinical School, Faculty of Medicine UNSW, Liverpool Hospital Liverpool New South Wales Australia.
³ Ingham Institute of Applied Medical Research Liverpool New South Wales Australia.
⁴ Department of Optometry and Vision Sciences University of Melbourne Melbourne Victoria Australia.
⁵ Department of Neurosurgery Maxine Dunitz Neurosurgical Research Institute and Department of Biomedical Sciences Cedars-Sinai Medical Center Los Angeles California USA.

Abstract

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 Aβ_1-40 and Aβ_1-42 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.

Keywords: APP/PS1 mice; Alzheimer's disease; amyloid beta oligomers; blood immunodetection; early Alzheimer's disease diagnosis; nanobodies; retinal immunodetection.