Retina and Brain Display Early and Differential Molecular and Cellular Changes in the 3xTg-AD Mouse Model of Alzheimer's Disease.

The concept 'the retina as a window to the brain' has been increasingly explored in Alzheimer´s disease (AD) in recent years, since some patients present visual alterations before the first symptoms of dementia. The retina is an extension of the brain and can be assessed by noninvasive methods. However, assessing the retina for AD diagnosis is still a matter of debate. Using the triple transgenic mouse model of AD (3xTg-AD; males), this study was undertaken to investigate whether the retina and brain (hippocampus and cortex) undergo similar molecular and cellular changes during the early stages (4 and 8 months) of the pathology, and if the retina can anticipate the alterations occurring in the brain. We assessed amyloid-beta (Aβ) and hyperphosphorylated tau (p-tau) levels, barrier integrity, cell death, neurotransmitter levels, and glial changes. Overall, the retina, hippocampus, and cortex of 3xTg-AD are not significantly affected at these early stages. However, we detected a few differential changes in the retina and brain regions, and particularly a different profile in microglia branching in the retina and hippocampus, only at 4 months, where the number and length of the processes decreased in the retina and increased in the hippocampus. In summary, at the early stages of pathology, the retina, hippocampus, and cortex are not significantly affected but already present some molecular and cellular alterations. The retina did not mirror the changes detected in the brain, and these observations should be taking into account when using the retina as a potential diagnostic tool for AD.