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The Retina as a Window or Mirror of the Brain Changes Detected in Alzheimer’s Disease: Critical Aspects to Unravel

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Abstract

Alzheimer’s disease is the most frequent cause of dementia worldwide, representing a global health challenge, with a massive impact on the quality of life of Alzheimer’s disease patients and their relatives. The diagnosis of Alzheimer’s disease constitutes a real challenge, because the symptoms manifest years after the first degenerative changes occurring in the brain and the diagnosis is based on invasive and/or expensive techniques. Therefore, there is an urgent need to identify new reliable biomarkers to detect Alzheimer’s disease at an early stage. Taking into account the evidence for visual deficits in Alzheimer’s disease patients, sometimes even before the appearance of the first disease symptoms, and that the retina is an extension of the brain, the concept of the retina as a window to look into the brain or a mirror of the brain has received increasing interest in recent years. However, only a few studies have assessed the changes occurring in the retina and the brain at the same time points. Unlike previous reviews on this subject, which are mainly focused on brain changes, we organized this review by comprehensively summarizing findings related with structural, functional, cellular, and molecular parameters in the retina reported in both Alzheimer’s disease patients and animal models. Moreover, we separated the studies that assessed only the retina, and those that assessed both the retina and brain, which are few but allow establishing correlations between the retina and brain. This review also highlights some inconsistent results in the literature as well as relevant missing gaps in this field.

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Funding

This work was supported by Santa Casa Mantero Belard Award 2015 (MB-1049-2015); Foundation for Science and Technology, PEst (UID/NEU/04539/2013); COMPETE-FEDER (POCI-01-0145-FEDER-007440); and Centro 2020 Regional Operational Programme (CENTRO-01-0145-FEDER-000008: BrainHealth 2020). Samuel Chiquita and Filipa I. Baptista acknowledge a fellowship from Foundation for Science and Technology, Portugal (SFRH/BD/52045/2012 and SFRH/BPD/86830/2012, respectively).

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  1. Samuel Chiquita and Ana C. Rodrigues-Neves contributed equally to this work.

Authors and Affiliations

  1. iCBR, Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Samuel Chiquita, Ana C. Rodrigues-Neves, Filipa I. Baptista, Rafael Carecho & António F. Ambrósio

  2. CNC.IBILI Consortium, University of Coimbra, Coimbra, Portugal

    Samuel Chiquita, Ana C. Rodrigues-Neves, Filipa I. Baptista, Rafael Carecho, Paula I. Moreira, Miguel Castelo-Branco & António F. Ambrósio

  3. CNC, Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

    Paula I. Moreira

  4. Institute of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Paula I. Moreira

  5. CIBIT, Coimbra Institute for Biomedical Imaging and Translational Research, ICNAS, Institute of Nuclear Sciences Applied to Health, University of Coimbra, Coimbra, Portugal

    Miguel Castelo-Branco

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Chiquita, S., Rodrigues-Neves, A.C., Baptista, F.I. et al. The Retina as a Window or Mirror of the Brain Changes Detected in Alzheimer’s Disease: Critical Aspects to Unravel. Mol Neurobiol 56, 5416–5435 (2019). https://doi.org/10.1007/s12035-018-1461-6

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