Evidence map›Paper›PMID 39187891›Full record

ArticleAlzheimer's research & therapy2024

Neurodegenerative biomarkers in different chambers of the eye relative to plasma: an agreement validation study.

Konstantina Sampani, Steven Ness, Fatima Tuz-Zahra, Nurgul Aytan, Elizabeth E Spurlock, Sreevardhan Alluri, Xuejing Chen, Nicole H Siegel, Michael L Alosco, Weiming Xia and 3 more

Abstract readValidation Study
In one paragraph

Article in Alzheimer's research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Konstantina Sampani *Beetham Eye Institute, Joslin Diabetes Center, Boston, MA, 02115, USA.
Steven Ness *Department of Ophthalmology, Boston Medical Center, Boston, MA, 02118, USA.
Fatima Tuz-ZahraDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Nurgul AytanBoston University Alzheimer's Disease Research Center and CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Elizabeth E SpurlockBoston University Alzheimer's Disease Research Center and CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Sreevardhan AlluriDepartment of Ophthalmology, Boston Medical Center, Boston, MA, 02118, USA.
Xuejing ChenDepartment of Ophthalmology, Boston Medical Center, Boston, MA, 02118, USA.
Nicole H SiegelDepartment of Ophthalmology, Boston Medical Center, Boston, MA, 02118, USA.
Michael L AloscoBoston University Alzheimer's Disease Research Center and CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Weiming XiaDepartment of Pharmacology and Experimental Therapeutics, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Yorghos TripodisDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Thor D Stein *Boston University Alzheimer's Disease Research Center and CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA. tdstein@bu.edu.
Manju L Subramanian *Department of Ophthalmology, Boston Medical Center, Boston, MA, 02118, USA. manju.subramanian@bmc.org.

Funding

RL5: Research Education CoreP30AG072978 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Lindsay A. Farrer · 2021 to 2026
$25.6M
Eye to Brain: Eye Biomarkers and CognitionR03AG063255 · NIA · BOSTON MEDICAL CENTER · PI SUBRAMANIAN, MANJU · 2019 to 2020
$371k
The neuropathology of mild traumatic brain injury in Alzheimer's diseaseI01BX005933 · VA · EDITH NOURSE ROGERS MEMORIAL VETERANS HOSPITAL · PI Thor Stein · 2023 to 2026
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BLRD VA I01 BX005933National Institute of Aging P30AG072978National Institute on Aging/NIH/DHHS 1R03AG063255-01NIA NIH HHS P30 AG072978NIA NIH HHS R03 AG063255United States Department of Veterans Affairs, Veterans Health Administration I01BX005933
6 · The paper itself

Abstract

backgroundProtein biomarkers have been broadly investigated in cerebrospinal fluid and blood for the detection of neurodegenerative diseases, yet a clinically useful diagnostic test to detect early, pre-symptomatic Alzheimer's disease (AD) remains elusive. We conducted this study to quantify Aβ40, Aβ42, total Tau (t-Tau), hyperphosphorylated Tau (ptau181), glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) in eye fluids relative to blood.

methodsIn this cross-sectional study we collected vitreous humor, aqueous humor, tear fluid and plasma in patients undergoing surgery for eye disease. All six biomarkers were quantitatively measured by digital immunoassay. Spearman and Bland-Altman correlation analyses were performed to assess the agreement of levels between ocular fluids and plasma.

resultsSeventy-nine adults underwent pars-plana vitrectomy in at least one eye. Of the 79, there were 77 vitreous, 67 blood, 56 tear fluid, and 51 aqueous samples. All six biomarkers were quantified in each bio-sample, except GFAP and NfL in tear fluid due to low sample volume. All six biomarkers were elevated in vitreous humor compared to plasma samples. T-Tau, ptau181, GFAP and NfL were higher in aqueous than in plasma, and t-Tau and ptau181 concentrations were higher in tear fluid than in plasma. Significant correlations were found between Aβ40 in plasma and tears (r = 0.5; p = 0.019), t-Tau in plasma and vitreous (r = 0.4; p = 0.004), NfL in plasma and vitreous (r = 0.3; p = 0.006) and plasma and aqueous (r = 0.5; p = 0.004). No significant associations were found for Aβ42, ptau181 and GFAP among ocular fluids relative to plasma. Bland-Altman analysis showed aqueous humor had the closest agreement to plasma across all biomarkers. Biomarker levels in ocular fluids revealed statistically significant associations between vitreous and aqueous for t-Tau (r = 0.5; p = 0.001), GFAP (r = 0.6; p < 0.001) and NfL (r = 0.7; p < 0.001).

conclusionAD biomarkers are detectable in greater quantities in eye fluids than in plasma and show correlations with levels in plasma. Future studies are needed to assess the utility of ocular fluid biomarkers as diagnostic and prognostic markers for AD, especially in those at risk with eye disease.

Indexed as

Amyloid beta-PeptidesAqueous HumorBiomarkersGlial Fibrillary Acidic ProteinNeurofilament Proteinstau ProteinsTearsVitreous BodyAdultAgedAged, 80 and overCross-Sectional StudiesFemaleHumansMaleMiddle AgedAmyloid beta-Peptidesamyloid beta-protein (1-42)BiomarkersGFAP protein, humanGlial Fibrillary Acidic Proteinneurofilament protein LNeurofilament ProteinsPeptide Fragmentstau ProteinsAlzheimer’s diseaseAmyloid betaAqueous humorGlial fibrillary acidic proteinNeurofilament light chainTauTearsVitreous humor

Identifiers

PMID39187891
PMCPMC11346268

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.