Structural and functional alterations in the retina of a model of Alzheimer’s disease and type 2 diabetes

The retina, as part of the central nervous system, shows abnormalities in Alzheimer`s disease (AD) and type 2 diabetes (T2D). Importantly, analysis of the retina may provide a non-invasive approach with diagnostic and prognostic value for cognitive decline. In addition, T2D increases risk to suffer AD. Accordingly, we have analyzed structural and functional alterations, by spectral domain optical coherence tomography and electroretinography (ERG) respectively, in the retina from APP/PS1 (AD model), db/db (T2D model) and APP/PS1xdb/db (AD-T2D model) animals at 4 weeks of age, before the onset of AD or T2D, and in 36-week-old mice, when both pathologies are chronic. APP/PS1xdb/db mice had significantly lower amplitude values in scotopic phase of ERG in 4- and 36-week-old mice. Photopic and flicker responses were also impaired in db/db animals at 36 weeks of age, and more severely in APP/PS1xdb/db mice. Also, APP/PS1xdb/db mice showed significant retinal thinning at 4 weeks of age, being more severe at 36 weeks. Further analysis revealed that inner retinal layers thickness was reduced in APP/PS1xdb/db mice, as early as 4 weeks of age, whereas abnormalities in outer retinal layers only were observed in diabetic mice at 36 weeks of age. Our data suggest structural and functional alterations of the retina appear as early as at 4 weeks of age when AD and T2 coexist, worsening when both pathologies are fully established. Funding: RECOGNISED (Clinical Trials gov registration no. NCT04281186) EuropeanCommission (H2020-GA847749). Ministerio de Ciencia e Innovación (PID2020-115499RB-I00). Plan Propio de la Universidad de Cádiz (PR2022-036).