Retinal nerve fiber layer thickness predicts CSF amyloid/tau before cognitive decline

• Published in: PloS one Vol. 15; no. 5; p. e0232785
• Main Authors: Asanad, Samuel, Fantini, Michele, Sultan, William, Nassisi, Marco, Felix, Christian M., Wu, Jessica, Karanjia, Rustum, Ross-Cisneros, Fred N., Sagare, Abhay P., Zlokovic, Berislav V., Chui, Helena C., Pogoda, Janice M., Arakaki, Xianghong, Fonteh, Alfred N., Sadun A. A., Alfredo A., Harrington, Michael G.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.05.2020; Public Library of Science (PLoS)
• Subjects: Aged; Aged, 80 and over; Algorithms; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - genetics; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - cerebrospinal fluid; Amyloid beta-Peptides - genetics; Amyloid beta-protein; Amyloidosis - cerebrospinal fluid; Amyloidosis - diagnostic imaging; Amyloidosis - genetics; Amyloidosis - pathology; Biology and Life Sciences; Biomarkers; Biomarkers - cerebrospinal fluid; Care and treatment; Cerebrospinal fluid; Cognitive ability; Cognitive Dysfunction - cerebrospinal fluid; Cognitive Dysfunction - diagnostic imaging; Cognitive Dysfunction - genetics; Cognitive Dysfunction - pathology; Correlation analysis; Dementia; Development and progression; Disease; Female; Geffen, David; Genetic aspects; Health aspects; Humans; Laboratories; Longitudinal studies; Male; Medical research; Medicine; Medicine and Health Sciences; Middle Aged; Nerve Fibers - metabolism; Nerve Fibers - pathology; Neurodegenerative diseases; Neurosciences; Ophthalmology; Optic Disk - diagnostic imaging; Optic Disk - metabolism; Optic Disk - pathology; Optical Coherence Tomography; Pathology; Physiology; Regression models; Research and Analysis Methods; Retina; Retina - diagnostic imaging; Retina - metabolism; Retina - pathology; Retinal Ganglion Cells - metabolism; Retinal Ganglion Cells - pathology; Sensitivity; Signs and symptoms; Standard error; Tau protein; Tau proteins; tau Proteins - cerebrospinal fluid; tau Proteins - genetics; Thickness; Tomography; Tomography, Optical Coherence; United States; Canada; Los Angeles California; Italy; Ottawa Ontario Canada; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0232785

Alzheimer's disease (AD) pathology precedes symptoms and its detection can identify at-risk individuals who may benefit from early treatment. Since the retinal nerve fiber layer (RNFL) is depleted in established AD, we tested whether its thickness can predict whether cognitively healthy (CH) individuals have a normal or pathological cerebrospinal fluid (CSF) Aß42 (A) and tau (T) ratio. As part of an ongoing longitudinal study, we enrolled CH individuals, excluding those with cognitive impairment and significant ocular pathology. We classified the CH group into two sub-groups, normal (CH-NAT, n = 16) or pathological (CH-PAT, n = 27), using a logistic regression model from the CSF AT ratio that identified >85% of patients with a clinically probable AD diagnosis. Spectral-domain optical coherence tomography (OCT) was acquired for RNFL, ganglion cell-inner plexiform layer (GC-IPL), and macular thickness. Group differences were tested using mixed model repeated measures and a classification model derived using multiple logistic regression. Mean age (± standard deviation) in the CH-PAT group (n = 27; 75.2 ± 8.4 years) was similar (p = 0.50) to the CH-NAT group (n = 16; 74.1 ± 7.9 years). Mean RNFL (standard error) was thinner in the CH-PAT group by 9.8 (2.7) μm; p < 0.001. RNFL thickness classified CH-NAT vs. CH-PAT with 87% sensitivity and 56.3% specificity. Our retinal data predict which individuals have CSF biomarkers of AD pathology before cognitive deficits are detectable with 87% sensitivity. Such results from easy-to-acquire, objective and non-invasive measurements of the RNFL merit further study of OCT technology to monitor or screen for early AD pathology.