TY - JOUR
T1 - Retinal changes in Alzheimer's disease— integrated prospects of imaging, functional and molecular advances
AU - Gupta, Veer B.
AU - Chitranshi, Nitin
AU - Haan, Jurre den
AU - Mirzaei, Mehdi
AU - You, Yuyi
AU - Lim, Jeremiah KH
AU - Basavarajappa, Devaraj
AU - Godinez, Angela
AU - Di Angelantonio, Silvia
AU - Sachdev, Perminder
AU - Salekdeh, Ghasem H.
AU - Bouwman, Femke
AU - Graham, Stuart
AU - Gupta, Vivek
PY - 2020/9/2
Y1 - 2020/9/2
N2 - Alzheimer's Disease (AD) is a devastating neurodegenerative disorder of the brain, clinically characterised by cognitive deficits that gradually worsen over time. There is, at present, no established cure, or disease-modifying treatments for AD. As life expectancy increases globally, the number of individuals suffering from the disease is projected to increase substantially. Cumulative evidence indicates that AD neuropathological process is initiated several years, if not decades, before clinical signs are evident in patients, and diagnosis made. While several imaging, cognitive, CSF and blood-based biomarkers have been proposed for the early detection of AD; their sensitivity and specificity in the symptomatic stages is highly variable and it is difficult to justify their use in even earlier, pre-clinical stages of the disease. Research has identified potentially measurable functional, structural, metabolic and vascular changes in the retina during early stages of AD. Retina offers a distinctively accessible insight into brain pathology and current and developing ophthalmic technologies have provided us with the possibility of detecting and characterising subtle, disease-related changes. Recent human and animal model studies have further provided mechanistic insights into the biochemical pathways that are altered in the retina in disease, including amyloid and tau deposition. This information coupled with advances in molecular imaging has allowed attempts to monitor biochemical changes and protein aggregation pathology in the retina in AD. This review summarises the existing knowledge that informs our understanding of the impact of AD on the retina and highlights some of the gaps that need to be addressed. Future research will integrate molecular imaging innovation with functional and structural changes to enhance our knowledge of the AD pathophysiological mechanisms and establish the utility of monitoring retinal changes as a potential biomarker for AD.
AB - Alzheimer's Disease (AD) is a devastating neurodegenerative disorder of the brain, clinically characterised by cognitive deficits that gradually worsen over time. There is, at present, no established cure, or disease-modifying treatments for AD. As life expectancy increases globally, the number of individuals suffering from the disease is projected to increase substantially. Cumulative evidence indicates that AD neuropathological process is initiated several years, if not decades, before clinical signs are evident in patients, and diagnosis made. While several imaging, cognitive, CSF and blood-based biomarkers have been proposed for the early detection of AD; their sensitivity and specificity in the symptomatic stages is highly variable and it is difficult to justify their use in even earlier, pre-clinical stages of the disease. Research has identified potentially measurable functional, structural, metabolic and vascular changes in the retina during early stages of AD. Retina offers a distinctively accessible insight into brain pathology and current and developing ophthalmic technologies have provided us with the possibility of detecting and characterising subtle, disease-related changes. Recent human and animal model studies have further provided mechanistic insights into the biochemical pathways that are altered in the retina in disease, including amyloid and tau deposition. This information coupled with advances in molecular imaging has allowed attempts to monitor biochemical changes and protein aggregation pathology in the retina in AD. This review summarises the existing knowledge that informs our understanding of the impact of AD on the retina and highlights some of the gaps that need to be addressed. Future research will integrate molecular imaging innovation with functional and structural changes to enhance our knowledge of the AD pathophysiological mechanisms and establish the utility of monitoring retinal changes as a potential biomarker for AD.
KW - Amyloid
KW - Dementia
KW - Glaucoma
KW - Hyperspectral imaging
KW - Imaging
KW - Neuroinflammation
KW - Optic nerve
KW - Optical coherence tomography (angiography)(OCTA)
KW - Proteomics
KW - Retina
KW - Retinal ganglion cell
KW - Tau
KW - Vascular changes
UR - http://www.scopus.com/inward/record.url?scp=85090553221&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/NHMRC/1136602
UR - http://purl.org/au-research/grants/NHMRC/1139560
U2 - 10.1016/j.preteyeres.2020.100899
DO - 10.1016/j.preteyeres.2020.100899
M3 - Review article
C2 - 32890742
AN - SCOPUS:85090553221
JO - Progress in Retinal and Eye Research
JF - Progress in Retinal and Eye Research
SN - 1350-9462
M1 - 100899
ER -