title: Beta-amyloid sequelae in the eye: a critical review on its diagnostic significance and clinical relevance in Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disorder. There is no test for its definitive diagnosis in routine clinical practice. Although phase III clinical trials have failed, only symptomatic treatment is currently available; a possible reason for these failed trials is that intervention commenced at an advanced stage of the disease. The hallmarks of an AD brain include plaques comprising of extracellular beta-amyloid (Aβ) protein aggregates and intracellular hyperphosphorylated neurofibrillary tangles of tau. Research into the preclinical diagnosis of AD has provided considerable evidence regarding early neuropathological changes using brain Aβ imaging and the cerebrospinal fluid biomarkers, Aβ and tau. Both these approaches have limitations that are expensive, invasive or time consuming and thus preclude them from screening at-risk population. Recent studies have demonstrated the presence of Aβ plaques in the eyes of AD subjects, which is positively associated with their brain Aβ burden. Thus ocular biomarkers point to a potential avenue for an earlier, relatively low-cost diagnosis in order for therapeutic interventions to be effective. Here we review the literature that spans the investigation for the presence of Aβ in aging eyes and the significance of its deposition in relation to AD pathology. We discuss clinical studies investigating in vivo imaging of Aβ in the eye and its association with brain Aβ burden and therapies that target ocular Aβ. Finally, we focus on the need to characterize AD-specific retinal Aβ to differentiate Aβ found in some eye diseases. Based on the current evidence, we conclude that integration of ocular biomarkers that can correctly predict brain Aβ burden would have an important role as a non-invasive, yet economical surrogate marker in the diagnostic process of AD.
authors.affiliation: Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, WA, Australia.|Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical Sciences, Edith Cowan University, Perth, WA, Australia.
authors.forename: T M
authors.initials: TM
authors.lastname: Shah
authors.affiliation: Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, WA, Australia.|Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical Sciences, Edith Cowan University, Perth, WA, Australia.
authors.forename: S M
authors.initials: SM
authors.lastname: Gupta
authors.affiliation: KaRa Institute of Neurological Diseases, Macquarie Park, NSW, Australia.|Australian School of Advanced Medicine, Faculty of Medicine and Health Sciences, Macquarie University, North Ryde, NSW, Australia.
authors.forename: P
authors.identifier: 0000-0003-4877-1958
authors.initials: P
authors.lastname: Chatterjee
authors.affiliation: Smurfit Institute of Genetics, Lincoln Place Gate, Trinity College Dublin, Dublin, Ireland.
authors.forename: M
authors.initials: M
authors.lastname: Campbell
authors.affiliation: Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, WA, Australia.|Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical Sciences, Edith Cowan University, Perth, WA, Australia.|KaRa Institute of Neurological Diseases, Macquarie Park, NSW, Australia.|Australian School of Advanced Medicine, Faculty of Medicine and Health Sciences, Macquarie University, North Ryde, NSW, Australia.|School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, WA, Australia.
authors.forename: R N
authors.initials: RN
authors.lastname: Martins
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000502:physiology; D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology; D009799:Ocular Physiological Phenomena / Q000235:genetics*; D058225:Plaque, Amyloid / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016875:tau Proteins