Table 2 Pathophysiological eye-brain connections

The eyes are described as ‘window to the brain’ based on many commonalities:

• Embryological: The retina and the brain both originate from the diencephalon during embryonic development and remain structurally and functionally connected throughout life.

• Anatomical: Both the retina and the brain are characterized by presence of a layered cytological structure, containing similarly structured neurons and axons, and a similar (micro)vascular structure that includes presence of a blood-retina/brain barrier,

• Physiological: The retina and the brain share multiple physiological processes, including neural processing, myelination by oligodendrocytes, and degenerative and regenerative processes.

Based on these commonalities, diseases affecting the brain can be expected to affect the eye and vice versa [36]. Indeed, ocular manifestations of AD are myriad and include retinal presence of AD pathology, neurodegeneration and changes in vasculature. Retinal AD pathology includes presence of amyloid peptides and plaques, vascular amyloid depositions, and tau pathology [42, 174, 175] which correlate with AD pathology burden in the brain and general cognition [42, 175]. For retinal neurodegenerative and vascular changes, the most extensively reviewed parameters are derived from OCT (e.g. retinal thinning and loss of retinal ganglion cells) and OCT-A (e.g. vessel density and tortuosity). These parameters generally differ between AD patients versus controls and correlate with cognition [14,15,16, 37,38,39]. Though the discriminative specificity for AD for single OCT and OCT-A parameters is debated, the retina can be imaged using a diverse array of non-invasive techniques, thereby providing access to a wide range of biomarkers that can serve as biomarkers to predict pathology in the brain.