TY - JOUR
T1 - Tear biomarkers for Alzheimer's disease screening and diagnosis (the TearAD study)
T2 - design and rationale of an observational longitudinal multicenter study
AU - van de Sande, Nienke
AU - Ramakers, Inez H. G. B.
AU - Visser, Pieter Jelle
AU - Verhey, Frans R. J.
AU - Verbraak, Frank D.
AU - Bouwman, Femke H.
AU - Berendschot, Tos T. J. M.
AU - Nuijts, Rudy M. M. A.
AU - Webers, Carroll A. B.
AU - Gijs, Marlies
N1 - Funding Information: The authors would like to thank Optina Diagnositics, specifically Shannon Campbell, Julie Antonelle Orellina, and Bastien St-Louis. The authors also would like to thank Merel van der Thiel and Dr. Jaap Jansen for help with participant recruitment and data collection through their GlyM study. Funding Information: This study was supported by a research grant from the NWO (Dutch Science Foundation) Veni Fellowship. Before granting funding, the funding body reviewed the study protocol. Publisher Copyright: © 2023, BioMed Central Ltd., part of Springer Nature.
PY - 2023/12
Y1 - 2023/12
N2 - 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).
AB - 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).
KW - Alzheimer’s disease
KW - Amyloid beta
KW - Biomarkers
KW - Cognition
KW - Dementia
KW - Neurofibrillary tangles
KW - Retinal nerve fiber layer
KW - Tear fluid
UR - http://www.scopus.com/inward/record.url?scp=85166598684&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s12883-023-03335-y
DO - https://doi.org/10.1186/s12883-023-03335-y
M3 - Article
C2 - 37543602
SN - 1471-2377
VL - 23
SP - 293
JO - BMC Neurology
JF - BMC Neurology
IS - 1
M1 - 293
ER -