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Tear biomarkers for Alzheimer’s disease screening and diagnosis (the TearAD study): design and rationale of an observational longitudinal multicenter study

BACKGROUND: Alzheimer’s disease (AD) is the most common cause of dementia, and due to increasing life expectancy the number of patients is expected to grow. The diagnosis of AD involves the use of biomarkers determined by an amyloid PET scan or cerebrospinal fluid analyses that are either invasive o...

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Autores principales: van de Sande, Nienke, Ramakers, Inez H. G. B., Visser, Pieter Jelle, Verhey, Frans R. J., Verbraak, Frank D., Bouwman, Femke H., Berendschot, Tos T. J. M., Nuijts, Rudy M. M. A., Webers, Carroll A. B., Gijs, Marlies
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10403876/
https://www.ncbi.nlm.nih.gov/pubmed/37543602
http://dx.doi.org/10.1186/s12883-023-03335-y
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author van de Sande, Nienke
Ramakers, Inez H. G. B.
Visser, Pieter Jelle
Verhey, Frans R. J.
Verbraak, Frank D.
Bouwman, Femke H.
Berendschot, Tos T. J. M.
Nuijts, Rudy M. M. A.
Webers, Carroll A. B.
Gijs, Marlies
author_facet van de Sande, Nienke
Ramakers, Inez H. G. B.
Visser, Pieter Jelle
Verhey, Frans R. J.
Verbraak, Frank D.
Bouwman, Femke H.
Berendschot, Tos T. J. M.
Nuijts, Rudy M. M. A.
Webers, Carroll A. B.
Gijs, Marlies
author_sort van de Sande, Nienke
collection PubMed
description BACKGROUND: Alzheimer’s disease (AD) is the most common cause of dementia, and due to increasing life expectancy the number of patients is expected to grow. The diagnosis of AD involves the use of biomarkers determined by an amyloid PET scan or cerebrospinal fluid analyses that are either invasive or expensive, and not available in each hospital, thus limiting their usage as a front-line screener. The TearAD study aims to use tear fluid as a potential source for AD biomarkers. In previous reports, we demonstrated that AD biomarkers amyloid-beta and tau, are measurable in tear fluid and are associated with disease severity and neurodegeration. This study aims to validate previous results in a larger cohort and evaluate the diagnostic accuracy of tear biomarkers to discriminate between individuals with and without neurodegeneration as determined by hippocampal atrophy. METHODS: The TearAD study is an observational longitudinal multi-center study that will enroll 50 cognitively healthy controls, 50 patients with subjective cognitive decline, 50 patients with mild cognitive impairment and 50 patients with AD dementia from the memory clinic. Participants will be examined at baseline, after one year, and after two years follow-up. Study assessments include neuropsychological tests and ophthalmic examination. All participants will receive a MRI scan, and a subset of the study population will undergo cerebral spinal fluid collection and an amyloid PET scan. Tear fluid will be collected with Schirmer strips and levels of Aβ38, Aβ40, Aβ42, t-tau and p-tau in tear fluid will be determined using multiplex immunoassays. Blood samples will be collected from all participants. Images of the retina will be obtained with a standard, hyperspectral and ultra-wide field fundus camera. Additionally, macular pigment optical density will be measured with the macular pigment reflectometer, and cross-sectional images of the retina will be obtained through optical coherence tomography imaging. DISCUSSION: The TearAD study will provide insight into the potential diagnostic use of tear biomarkers as a minimally invasive and low cost tool for the screening and diagnosis of AD. TRIAL REGISTRATION: Retrospectively registered at clinicaltrials.gov (NCT05655793).
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spelling pubmed-104038762023-08-06 Tear biomarkers for Alzheimer’s disease screening and diagnosis (the TearAD study): design and rationale of an observational longitudinal multicenter study van de Sande, Nienke Ramakers, Inez H. G. B. Visser, Pieter Jelle Verhey, Frans R. J. Verbraak, Frank D. Bouwman, Femke H. Berendschot, Tos T. J. M. Nuijts, Rudy M. M. A. Webers, Carroll A. B. Gijs, Marlies BMC Neurol Study Protocol BACKGROUND: Alzheimer’s disease (AD) is the most common cause of dementia, and due to increasing life expectancy the number of patients is expected to grow. The diagnosis of AD involves the use of biomarkers determined by an amyloid PET scan or cerebrospinal fluid analyses that are either invasive or expensive, and not available in each hospital, thus limiting their usage as a front-line screener. The TearAD study aims to use tear fluid as a potential source for AD biomarkers. In previous reports, we demonstrated that AD biomarkers amyloid-beta and tau, are measurable in tear fluid and are associated with disease severity and neurodegeration. This study aims to validate previous results in a larger cohort and evaluate the diagnostic accuracy of tear biomarkers to discriminate between individuals with and without neurodegeneration as determined by hippocampal atrophy. METHODS: The TearAD study is an observational longitudinal multi-center study that will enroll 50 cognitively healthy controls, 50 patients with subjective cognitive decline, 50 patients with mild cognitive impairment and 50 patients with AD dementia from the memory clinic. Participants will be examined at baseline, after one year, and after two years follow-up. Study assessments include neuropsychological tests and ophthalmic examination. All participants will receive a MRI scan, and a subset of the study population will undergo cerebral spinal fluid collection and an amyloid PET scan. Tear fluid will be collected with Schirmer strips and levels of Aβ38, Aβ40, Aβ42, t-tau and p-tau in tear fluid will be determined using multiplex immunoassays. Blood samples will be collected from all participants. Images of the retina will be obtained with a standard, hyperspectral and ultra-wide field fundus camera. Additionally, macular pigment optical density will be measured with the macular pigment reflectometer, and cross-sectional images of the retina will be obtained through optical coherence tomography imaging. DISCUSSION: The TearAD study will provide insight into the potential diagnostic use of tear biomarkers as a minimally invasive and low cost tool for the screening and diagnosis of AD. TRIAL REGISTRATION: Retrospectively registered at clinicaltrials.gov (NCT05655793). BioMed Central 2023-08-05 /pmc/articles/PMC10403876/ /pubmed/37543602 http://dx.doi.org/10.1186/s12883-023-03335-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Study Protocol
van de Sande, Nienke
Ramakers, Inez H. G. B.
Visser, Pieter Jelle
Verhey, Frans R. J.
Verbraak, Frank D.
Bouwman, Femke H.
Berendschot, Tos T. J. M.
Nuijts, Rudy M. M. A.
Webers, Carroll A. B.
Gijs, Marlies
Tear biomarkers for Alzheimer’s disease screening and diagnosis (the TearAD study): design and rationale of an observational longitudinal multicenter study
title Tear biomarkers for Alzheimer’s disease screening and diagnosis (the TearAD study): design and rationale of an observational longitudinal multicenter study
title_full Tear biomarkers for Alzheimer’s disease screening and diagnosis (the TearAD study): design and rationale of an observational longitudinal multicenter study
title_fullStr Tear biomarkers for Alzheimer’s disease screening and diagnosis (the TearAD study): design and rationale of an observational longitudinal multicenter study
title_full_unstemmed Tear biomarkers for Alzheimer’s disease screening and diagnosis (the TearAD study): design and rationale of an observational longitudinal multicenter study
title_short Tear biomarkers for Alzheimer’s disease screening and diagnosis (the TearAD study): design and rationale of an observational longitudinal multicenter study
title_sort tear biomarkers for alzheimer’s disease screening and diagnosis (the tearad study): design and rationale of an observational longitudinal multicenter study
topic Study Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10403876/
https://www.ncbi.nlm.nih.gov/pubmed/37543602
http://dx.doi.org/10.1186/s12883-023-03335-y
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