Relationships between longitudinal retinal amyloid imaging and amyloid PET in the A4 Trial

Sonal Sukreet; Michael C. Donohue; Jennifer Ngolab; Alison Belsha; Jennifer Salazar; Paula Cohen; Sandhya Jaiswal; Veasna Tan; Neelum T. Aggarwal; Jessica Alber; Ken Johnson; Gregory A. Jicha; Christopher H. van Dyck; Srinath Ramanan; James J. Lah; Stephen Salloway; Steven R. Verdooner; Michael S. Rafii; Paul S. Aisen; Reisa A. Sperling; Robert A. Rissman

doi:10.1002/dad2.70422

Relationships between longitudinal retinal amyloid imaging and amyloid PET in the A4 Trial

Sonal Sukreet
, Michael C. Donohue
, Jennifer Ngolab
, Alison Belsha
, Jennifer Salazar
, Paula Cohen
, Sandhya Jaiswal
, Veasna Tan
, Neelum T. Aggarwal
, Jessica Alber
, Ken Johnson
, Gregory A. Jicha
, Christopher H. van Dyck
, Srinath Ramanan
, James J. Lah
, Stephen Salloway
, Steven R. Verdooner
, Michael S. Rafii
, Paul S. Aisen
, Reisa A. Sperling

Robert A. Rissman

Research output: Contribution to journal › Article › peer-review

Abstract

INTRODUCTION: Alzheimer's disease (AD) is associated with retinal amyloid-related changes, which may help identify amyloid positron emission tomography (PET) positive (+) individuals. Previously, in a small cross-sectional study, we reported higher retinal spot counts (RSCs) in preclinical amyloid PET (+) individuals screened for the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) trial compared to control individuals enrolled in the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) trial before drug treatment. METHODS: Eligible volunteers had retinal scans 48 hours after consuming curcumin. Scans were processed and quantified via NeuroVision. Participants were grouped by amyloid status and treatment to assess the effect of solanezumab on RSC. RESULTS: RSC did not differ significantly over time between groups and was not modified by treatment, diverging from the cross-sectional retinal amyloid findings observed in A4/LEARN. DISCUSSION: Curcumin-based retinal amyloid labeling shows promise but needs standardized protocols and validation in larger cohorts to understand its relationship to amyloid PET.

Original language	English
Article number	e70422
Journal	Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Volume	18
Issue number	3
DOIs	https://doi.org/10.1002/dad2.70422
State	Published - Jul 1 2026

Bibliographical note

Publisher Copyright:
© 2026 The Author(s). Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Funding

The authors thank the members of Rissman Lab at USC's Epstein Family Alzheimer's Therapeutic Research Institute in San Diego for their help and suggestions. We would like to extend our gratitude and acknowledge the dedication of all participants, site personnel, and partnership team members who continue to make the A4 study possible. The A4 and LEARN Studies were supported by a public–private–philanthropic partnership which included funding from the National Institute on Aging of the National Institutes of Health (R01 AG063689, U19AG010483 and U24AG057437), Eli Lilly (also the supplier of active medication and placebo), the Alzheimer's Association, the Accelerating Medicines Partnership through the Foundation for the National Institutes of Health, the GHR Foundation, the Davis Alzheimer Prevention Program, the Yugilbar Foundation, an anonymous foundation, and additional private donors to Brigham and Women's Hospital, with in-kind support from Avid Radiopharmaceuticals, Cogstate, Albert Einstein College of Medicine, and the Foundation for Neurologic Diseases. The complete A4 study team list is available at: a4study.org/a4-study-team.

Funders	Funder number
Alzheimer's Association
Yugilbar Foundation
Eli Lilly and Company
Foundation for Neurologic Diseases
GHR Foundation
U.S. Department of Health & Human Services \| NIH \| National Institute on Aging (U.S. National Institute on Aging)
National Institutes of Health (NIH)	U19AG010483, U24AG057437, R01 AG063689

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Alzheimer's disease
NeuroVision
amyloid
positron emission tomography
retina
retinopathy

ASJC Scopus subject areas

Clinical Neurology
Psychiatry and Mental health

Access to Document

10.1002/dad2.70422

Cite this

Sukreet, S., Donohue, M. C., Ngolab, J., Belsha, A., Salazar, J., Cohen, P., Jaiswal, S., Tan, V., Aggarwal, N. T., Alber, J., Johnson, K., Jicha, G. A., van Dyck, C. H., Ramanan, S., Lah, J. J., Salloway, S., Verdooner, S. R., Rafii, M. S., Aisen, P. S., ... Rissman, R. A. (2026). Relationships between longitudinal retinal amyloid imaging and amyloid PET in the A4 Trial. Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, 18(3), Article e70422. https://doi.org/10.1002/dad2.70422

@article{204ec4cafd6c4c858c468035460cb3e1,

title = "Relationships between longitudinal retinal amyloid imaging and amyloid PET in the A4 Trial",

abstract = "INTRODUCTION: Alzheimer's disease (AD) is associated with retinal amyloid-related changes, which may help identify amyloid positron emission tomography (PET) positive (+) individuals. Previously, in a small cross-sectional study, we reported higher retinal spot counts (RSCs) in preclinical amyloid PET (+) individuals screened for the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) trial compared to control individuals enrolled in the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) trial before drug treatment. METHODS: Eligible volunteers had retinal scans 48 hours after consuming curcumin. Scans were processed and quantified via NeuroVision. Participants were grouped by amyloid status and treatment to assess the effect of solanezumab on RSC. RESULTS: RSC did not differ significantly over time between groups and was not modified by treatment, diverging from the cross-sectional retinal amyloid findings observed in A4/LEARN. DISCUSSION: Curcumin-based retinal amyloid labeling shows promise but needs standardized protocols and validation in larger cohorts to understand its relationship to amyloid PET.",

keywords = "Alzheimer's disease, NeuroVision, amyloid, positron emission tomography, retina, retinopathy",

author = "Sonal Sukreet and Donohue, \{Michael C.\} and Jennifer Ngolab and Alison Belsha and Jennifer Salazar and Paula Cohen and Sandhya Jaiswal and Veasna Tan and Aggarwal, \{Neelum T.\} and Jessica Alber and Ken Johnson and Jicha, \{Gregory A.\} and \{van Dyck\}, \{Christopher H.\} and Srinath Ramanan and Lah, \{James J.\} and Stephen Salloway and Verdooner, \{Steven R.\} and Rafii, \{Michael S.\} and Aisen, \{Paul S.\} and Sperling, \{Reisa A.\} and Rissman, \{Robert A.\}",

note = "Publisher Copyright: {\textcopyright} 2026 The Author(s). Alzheimer's \& Dementia: Diagnosis, Assessment \& Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2026",

month = jul,

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doi = "10.1002/dad2.70422",

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Sukreet, S, Donohue, MC, Ngolab, J, Belsha, A, Salazar, J, Cohen, P, Jaiswal, S, Tan, V, Aggarwal, NT, Alber, J, Johnson, K, Jicha, GA, van Dyck, CH, Ramanan, S, Lah, JJ, Salloway, S, Verdooner, SR, Rafii, MS, Aisen, PS, Sperling, RA & Rissman, RA 2026, 'Relationships between longitudinal retinal amyloid imaging and amyloid PET in the A4 Trial', Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, vol. 18, no. 3, e70422. https://doi.org/10.1002/dad2.70422

TY - JOUR

T1 - Relationships between longitudinal retinal amyloid imaging and amyloid PET in the A4 Trial

AU - Sukreet, Sonal

AU - Donohue, Michael C.

AU - Ngolab, Jennifer

AU - Belsha, Alison

AU - Salazar, Jennifer

AU - Cohen, Paula

AU - Jaiswal, Sandhya

AU - Tan, Veasna

AU - Aggarwal, Neelum T.

AU - Alber, Jessica

AU - Johnson, Ken

AU - Jicha, Gregory A.

AU - van Dyck, Christopher H.

AU - Ramanan, Srinath

AU - Lah, James J.

AU - Salloway, Stephen

AU - Verdooner, Steven R.

AU - Rafii, Michael S.

AU - Aisen, Paul S.

AU - Sperling, Reisa A.

AU - Rissman, Robert A.

PY - 2026/7/1

Y1 - 2026/7/1

N2 - INTRODUCTION: Alzheimer's disease (AD) is associated with retinal amyloid-related changes, which may help identify amyloid positron emission tomography (PET) positive (+) individuals. Previously, in a small cross-sectional study, we reported higher retinal spot counts (RSCs) in preclinical amyloid PET (+) individuals screened for the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) trial compared to control individuals enrolled in the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) trial before drug treatment. METHODS: Eligible volunteers had retinal scans 48 hours after consuming curcumin. Scans were processed and quantified via NeuroVision. Participants were grouped by amyloid status and treatment to assess the effect of solanezumab on RSC. RESULTS: RSC did not differ significantly over time between groups and was not modified by treatment, diverging from the cross-sectional retinal amyloid findings observed in A4/LEARN. DISCUSSION: Curcumin-based retinal amyloid labeling shows promise but needs standardized protocols and validation in larger cohorts to understand its relationship to amyloid PET.

AB - INTRODUCTION: Alzheimer's disease (AD) is associated with retinal amyloid-related changes, which may help identify amyloid positron emission tomography (PET) positive (+) individuals. Previously, in a small cross-sectional study, we reported higher retinal spot counts (RSCs) in preclinical amyloid PET (+) individuals screened for the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) trial compared to control individuals enrolled in the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) trial before drug treatment. METHODS: Eligible volunteers had retinal scans 48 hours after consuming curcumin. Scans were processed and quantified via NeuroVision. Participants were grouped by amyloid status and treatment to assess the effect of solanezumab on RSC. RESULTS: RSC did not differ significantly over time between groups and was not modified by treatment, diverging from the cross-sectional retinal amyloid findings observed in A4/LEARN. DISCUSSION: Curcumin-based retinal amyloid labeling shows promise but needs standardized protocols and validation in larger cohorts to understand its relationship to amyloid PET.

KW - Alzheimer's disease

KW - NeuroVision

KW - amyloid

KW - positron emission tomography

KW - retina

KW - retinopathy

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UR - https://www.scopus.com/pages/publications/105044226540#tab=citedBy

U2 - 10.1002/dad2.70422

DO - 10.1002/dad2.70422

M3 - Article

AN - SCOPUS:105044226540

VL - 18

JO - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring

JF - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring

IS - 3

M1 - e70422

ER -

Relationships between longitudinal retinal amyloid imaging and amyloid PET in the A4 Trial

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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