The Eye as a Diagnostic Tool for Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder impacting cognition, function, and behavior in the elderly population. While there are currently no disease-modifying agents capable of curing AD, early diagnosis and management in the preclinical stage can significantly improve patient morbidity and life expectancy. Currently, the diagnosis of Alzheimer’s disease is a clinical one, often supplemented by invasive and expensive biomarker testing. Over the last decade, significant advancements have been made in our understanding of AD and the role of ocular tissue as a potential biomarker. Ocular biomarkers hold the potential to provide noninvasive and easily accessible diagnostic and monitoring capabilities. This review summarizes current research for detecting biomarkers of Alzheimer’s disease in ocular tissue.

Alzheimer's Disease Diagnosis in the Preclinical Stage: Normal Aging or Dementia

“…It is also worth noting that despite recent findings in AD fluid biomarkers, the cross-talk of Aβ-tau proteins and mechanisms underlying neuronal injury and inflammation in cognitive decline are not fully understood. Because of that, [54] Changes in eye tissue characteristics (particularly in the retina and cornea): thinner nerve fiber layer, abnormalities in retinal capillary levels, vasculature changes, reduced metabolic activity [18] -Dynamic intraocular and extraocular behaviors: pupillary dilation and eye blink rate (BR) [17,55] -Oculomotor behavior changes [17,55] : 1-saccadic movements 2-smooth pursuit 3-reduction in eye movement velocity Physical behaviors -Motor dysfunction symptoms: 1-Changes in body movement symptoms: -impaired gait quantified by various parameters, such as stride length, step rate, velocity, and cadence, particularly stride-to-stride feature [56] and toe off -slow walking, poor balance, disability of fine motor skills [57] -declines in finger and hand skills, Low handgrip strength [58] 2-Changes in physical activities like increased duration of sedentary activity [59] 3-Head turning sign (HTS) [60]…”

“…Moreover, eye blink rate (BR) can be an extraocular noninvasive candidate to reveal mild cognitive impairment. Elevated blink rate may potentially serve as an early symptom preceding the progression of Alzheimer's disease [55,67].…”

Ferritin nanocage-enabled detection of pathological tau in living human retinal cells

“…In this framework, markers that are able to directly correlate brain aggregates with clinical AD manifestation are long-awaited for the AD diagnostics and follow-up. In contrast to the brain, the retina is unique in that it can be visualized in vivo using optical imaging methods, such as fundus photography (FP), optical coherence tomography (OCT), OCT‐angiography (OCT‐A), fluorescence lifetime imaging ophthalmoscopy (FLIO), and hyperspectral imaging (HSI) 8 – 13 . Thus far, retinal imaging represents a window of opportunity to assess neurodegenerative AD, through the eye 13 – 16 .…”

Early ultrasonic vocalization deficits and related thyroarytenoid muscle pathology in the transgenic TgF344-AD rat model of Alzheimer’s disease

“…Specifically, some of the earliest communication changes in prodromal AD are characterized by subtle changes to temporal speech parameters in individuals who are clinically unimpaired, but show evidence of abnormal, global β-amyloid and/or tau deposition ( Mueller et al, 2016 , 2018a , b , 2021 ; Mazzon et al, 2019 ; Hajjar et al, 2023 ). Despite recent attention to novel brain ( Jack et al, 2018 ; van Oostveen and de Lange, 2021 ; Ardanaz et al, 2022 ; Uchida, 2022 ; Veitch et al, 2022 ; Leuzy et al, 2022b ), peripheral ( Mantzavinos and Alexiou, 2017 ; Xie et al, 2022 ), and early behavioral biomarkers ( Li et al, 2017 ; Patel and Masurkar, 2021 ; Zhang et al, 2022 ; Hussain et al, 2023 ), communication often remains overlooked as a potential target for AD detection.…”