All cells in the body contain building blocks called proteins. In many neurodegenerative diseases, certain proteins are known to form abnormal clumps in the brain. One such protein in Alzheimer’s disease is called amyloid beta. Amyloid beta is a small, sticky fragment of protein. These small fragments stick together, and can form small clusters called oligomers, or large clumps called plaques. Previous work has shown that amyloid beta oligomers can be detected in the blood before clinical symptoms of Alzheimer’s are present.
One of the early issues often noted in Alzheimer’s is changes to vision including alterations in colour vision, sensitivity, nerve damage, and loss of cells in the eye. Amyloid beta deposits have previously been seen in the retina, both in people with Alzheimer’s and various animal models.
This study used small molecules known as ‘nanobodies’ to detect amyloid beta oligomers and plaques in the eye and brain of a mouse model of Alzheimer’s, to investigate where amyloid beta appears first, and when this occurs in relation to behavioural and memory symptoms in the mice. These mice have been given certain genes, blueprints which determine all our traits, which are associated with Alzheimer’s. This causes the mice to mimic certain biological and behavioural aspects of Alzheimer’s. Behavioural symptoms are usually seen at around 7 months, though this was not specifically tested in this study.
When the mice were 3 months of age, amyloid beta oligomers were seen in the eye, but not the brain. This suggests that the presence of amyloid beta in the eye precedes accumulation in the brain. No plaques were seen in either the brain or the eye at this age. By 8 months of age, oligomers were detectable in the brain as well as the eye, and plaques had begun to form in both. At 18 months, oligomers were no longer detectable in either the eye or the brain, but plaques had become more widespread. Neither oligomers nor plaques were seen at any age in non-Alzheimer’s mice. This data shows that amyloid beta oligomers appear in the eye months before they appear in the brain, and that plaques increase over the course of Alzheimer’s, whilst oligomers decrease.
The study then went on to investigate the presence of amyloid beta in the blood, and whether this occurred at the same time as detection of amyloid beta in the eye. Amyloid beta oligomers were seen in the blood of 3-month-old mice, suggesting that they appear in the blood either before or at the same time as in the eye.
The study also examined the localisation of oligomers and plaques within the brain and the eye, and found they occurred together. This adds support to the theory that oligomers are converted into plaques as Alzheimer’s progresses, though further research is needed to confirm this.
Finding simple ways to diagnose Alzheimer’s earlier is a key area of research. This study found that in a mouse model of Alzheimer’s, amyloid beta oligomers are present in the blood and the eye before oligomers or plaques are detected in the brain. This also occurred before memory and behavioural changes are usually seen in these mice. This raises the question of whether testing for amyloid beta oligomers in the eye and/or blood could be a potential diagnostic tool in clinical practice, which could lead to earlier therapeutic intervention, increasing the chances of slowing the progression of Alzheimer’s. However, further research is needed to confirm these findings, as well as identify if similar processes occur in human Alzheimer’s.