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Cerebrospinal fluid amyloid-β 42/40 ratio is associated with ganglion cell-inner plexiform layer thinning in individuals with and without amyloid pathology.

Publication ,  Journal Article
Patel, H; Choi, A; Weng, P; Karl, J; Joseph, S; Johnson, KG; Berger, M; Whitson, HE; Grewal, DS; Fekrat, S
Published in: J Alzheimers Dis
April 2026

BackgroundRetinal imaging offers a noninvasive window into neurodegenerative changes, yet its relationship with established cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) remains poorly understood. This study addresses a critical gap by examining whether retinal structural findings on optical coherence tomography (OCT) correlate with CSF biomarkers of AD pathology and neurodegeneration.ObjectiveTo determine if CSF biomarkers correlate with retinal OCT imaging findings in individuals with AD.MethodsIn this cross-sectional study, subjects underwent lumbar puncture for CSF collection and were imaged using the Zeiss Cirrus HD-5000 with AngioPlex.ResultsForty participants (73 eyes) were included in this study. Twenty-one had normal cognition and negative CSF AD biomarkers, 12 had normal cognition and positive CSF AD biomarkers, and seven had mild cognitive impairment. Central subfield thickness (CST), retinal nerve fiber layer (RNFL), and ganglion cell inner plexiform layer (GCIPL) thicknesses were associated with CSF amyloid-β 42/40 ratio (Aβ42/40), phosphorylated tau at threonine 181 (pTau181)/Aβ40 ratio, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) using multivariable generalized estimating equations. There were no statistically significant associations between CSF pTau181/Aβ40 ratio, NfL, or GFAP and CST, GCIPL thickness, or RNFL thickness (p > 0.05 for all). Aβ42/40 ratio was positively associated with GCIPL thickness (p = 0.02), but not with CST or RNFL thickness (p = 0.31 and p = 0.82, respectively).ConclusionsDecreased CSF Aβ42/40 ratio, a biomarker of amyloid plaque pathology, is associated with decreased GCIPL thickness. GCIPL thinning may correspond with CSF abnormalities consistent with amyloid pathology that is present even prior to cognitive decline.

Duke Scholars

Published In

J Alzheimers Dis

DOI

EISSN

1875-8908

Publication Date

April 2026

Volume

110

Issue

3

Start / End Page

1438 / 1446

Location

United States

Related Subject Headings

  • tau Proteins
  • Tomography, Optical Coherence
  • Retinal Ganglion Cells
  • Peptide Fragments
  • Neurology & Neurosurgery
  • Neurofilament Proteins
  • Middle Aged
  • Male
  • Humans
  • Glial Fibrillary Acidic Protein
 

Citation

APA
Chicago
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MLA
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Patel, H., Choi, A., Weng, P., Karl, J., Joseph, S., Johnson, K. G., … Fekrat, S. (2026). Cerebrospinal fluid amyloid-β 42/40 ratio is associated with ganglion cell-inner plexiform layer thinning in individuals with and without amyloid pathology. J Alzheimers Dis, 110(3), 1438–1446. https://doi.org/10.1177/13872877261423968
Patel, Hemal, Alex Choi, Peter Weng, Jamie Karl, Suzanna Joseph, Kim G. Johnson, Miles Berger, Heather E. Whitson, Dilraj S. Grewal, and Sharon Fekrat. “Cerebrospinal fluid amyloid-β 42/40 ratio is associated with ganglion cell-inner plexiform layer thinning in individuals with and without amyloid pathology.J Alzheimers Dis 110, no. 3 (April 2026): 1438–46. https://doi.org/10.1177/13872877261423968.
Patel H, Choi A, Weng P, Karl J, Joseph S, Johnson KG, et al. Cerebrospinal fluid amyloid-β 42/40 ratio is associated with ganglion cell-inner plexiform layer thinning in individuals with and without amyloid pathology. J Alzheimers Dis. 2026 Apr;110(3):1438–46.
Patel, Hemal, et al. “Cerebrospinal fluid amyloid-β 42/40 ratio is associated with ganglion cell-inner plexiform layer thinning in individuals with and without amyloid pathology.J Alzheimers Dis, vol. 110, no. 3, Apr. 2026, pp. 1438–46. Pubmed, doi:10.1177/13872877261423968.
Patel H, Choi A, Weng P, Karl J, Joseph S, Johnson KG, Berger M, Whitson HE, Grewal DS, Fekrat S. Cerebrospinal fluid amyloid-β 42/40 ratio is associated with ganglion cell-inner plexiform layer thinning in individuals with and without amyloid pathology. J Alzheimers Dis. 2026 Apr;110(3):1438–1446.

Published In

J Alzheimers Dis

DOI

EISSN

1875-8908

Publication Date

April 2026

Volume

110

Issue

3

Start / End Page

1438 / 1446

Location

United States

Related Subject Headings

  • tau Proteins
  • Tomography, Optical Coherence
  • Retinal Ganglion Cells
  • Peptide Fragments
  • Neurology & Neurosurgery
  • Neurofilament Proteins
  • Middle Aged
  • Male
  • Humans
  • Glial Fibrillary Acidic Protein