PMID- 32469871 OWN - NLM STAT- MEDLINE DCOM- 20200731 LR - 20240426 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 15 IP - 5 DP - 2020 TI - Retinal nerve fiber layer thickness predicts CSF amyloid/tau before cognitive decline. PG - e0232785 LID - 10.1371/journal.pone.0232785 [doi] LID - e0232785 AB - BACKGROUND: 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. METHODS: 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. RESULTS: 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) mum; p < 0.001. RNFL thickness classified CH-NAT vs. CH-PAT with 87% sensitivity and 56.3% specificity. CONCLUSIONS: 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. FAU - Asanad, Samuel AU - Asanad S AD - Doheny Eye Institute, Los Angeles, CA, United States of America. AD - Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America. FAU - Fantini, Michele AU - Fantini M AD - Doheny Eye Institute, Los Angeles, CA, United States of America. AD - Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America. AD - Department of Medicine, Ophthalmology, University of Udine, Udine, Italy. FAU - Sultan, William AU - Sultan W AD - Doheny Eye Institute, Los Angeles, CA, United States of America. FAU - Nassisi, Marco AU - Nassisi M AD - Doheny Eye Institute, Los Angeles, CA, United States of America. AD - Department of Clinical Sciences and Community Health, Ophthalmological Unit, IRCCS-Ca Granda Foundation-Ospedale Maggiore Policlinico, University of Milan, Milan, Italy. FAU - Felix, Christian M AU - Felix CM AD - Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America. FAU - Wu, Jessica AU - Wu J AD - Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America. FAU - Karanjia, Rustum AU - Karanjia R AD - Doheny Eye Institute, Los Angeles, CA, United States of America. AD - Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America. AD - Department of Ophthalmology, University of Ottawa, Ottawa, Ontario, Canada. AD - Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. FAU - Ross-Cisneros, Fred N AU - Ross-Cisneros FN AD - Doheny Eye Institute, Los Angeles, CA, United States of America. FAU - Sagare, Abhay P AU - Sagare AP AD - Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States of America. FAU - Zlokovic, Berislav V AU - Zlokovic BV AD - Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States of America. FAU - Chui, Helena C AU - Chui HC AD - Department of Neurology, University of Southern California, Los Angeles, CA, United States of America. FAU - Pogoda, Janice M AU - Pogoda JM AD - Cipher Biostatistics & Reporting, Reno, NV, United States of America. FAU - Arakaki, Xianghong AU - Arakaki X AD - Huntington Medical Research Institutes, Pasadena, CA, United States of America. FAU - Fonteh, Alfred N AU - Fonteh AN AD - Huntington Medical Research Institutes, Pasadena, CA, United States of America. FAU - Sadun, Alfredo A AU - Sadun AA AD - Doheny Eye Institute, Los Angeles, CA, United States of America. AD - Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America. FAU - Harrington, Michael G AU - Harrington MG AUID- ORCID: 0000-0002-7923-8032 AD - Huntington Medical Research Institutes, Pasadena, CA, United States of America. LA - eng GR - P01 AG052350/AG/NIA NIH HHS/United States GR - P50 AG005142/AG/NIA NIH HHS/United States GR - UL1 TR001855/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200529 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Amyloid beta-Peptides) RN - 0 (Biomarkers) RN - 0 (tau Proteins) SB - IM EIN - PLoS One. 2020 Jul 14;15(7):e0236379. PMID: 32663228 MH - Aged MH - Aged, 80 and over MH - Alzheimer Disease/cerebrospinal fluid/diagnostic imaging/*genetics/pathology MH - Amyloid beta-Peptides/cerebrospinal fluid/*genetics MH - Amyloidosis/cerebrospinal fluid/diagnostic imaging/genetics/pathology MH - Biomarkers/cerebrospinal fluid MH - Cognitive Dysfunction/cerebrospinal fluid/diagnostic imaging/*genetics/pathology MH - Female MH - Humans MH - Male MH - Middle Aged MH - Nerve Fibers/metabolism/pathology MH - Optic Disk/diagnostic imaging/metabolism/pathology MH - Retina/diagnostic imaging/metabolism/pathology MH - Retinal Ganglion Cells/metabolism/pathology MH - Tomography, Optical Coherence MH - tau Proteins/cerebrospinal fluid/*genetics PMC - PMC7259639 COIS- The authors have declared that no competing interests exist. EDAT- 2020/05/30 06:00 MHDA- 2020/08/01 06:00 PMCR- 2020/05/29 CRDT- 2020/05/30 06:00 PHST- 2020/01/23 00:00 [received] PHST- 2020/04/21 00:00 [accepted] PHST- 2020/05/30 06:00 [entrez] PHST- 2020/05/30 06:00 [pubmed] PHST- 2020/08/01 06:00 [medline] PHST- 2020/05/29 00:00 [pmc-release] AID - PONE-D-20-02170 [pii] AID - 10.1371/journal.pone.0232785 [doi] PST - epublish SO - PLoS One. 2020 May 29;15(5):e0232785. doi: 10.1371/journal.pone.0232785. eCollection 2020.