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Neurovascular Outer Retinal Degeneration in Presymptomatic Alzheimer’s Disease: An Oculomic Biomarker Study
Chan JW, Corradetti G, Soylu C, Almidani L, Wu X, Wang ZC, Astraea N, Hu Z et al.. Research Square, 2026-07-15
Topic: Plasma and spinal-fluid biomarkers
Background Noninvasive biomarkers reflecting early Alzheimer’s disease (AD) pathophysiology are critically needed. The retina, as an extension of the central nervous system, provides a unique oculomic platform to interrogate neurodegeneration. We evaluated whether retinal microvascular changes are spatially linked with neuronal structural degeneration in cognitively normal individuals at risk for AD within an amyloid (A) / tau (T) / neurodegeneration (N) / vascular (V) biomarker framework. Methods In this cross-sectional study, cognitively normal older adults with abnormal plasma Aβ42/40 ratios and normal ptau217 levels underwent multimodal retinal imaging using optical coherence tomography (OCT) and OCT angiography (OCTA). Choriocapillaris flow deficit percentage (CCFD%) and outer retinal layer thicknesses were quantified across the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Associations between regional vascular impairment and co-localized neuronal structural changes were analyzed using age-adjusted models accounting for inter-eye correlation. Results Increased CCFD% was significantly associated with localized thinning of photoreceptor inner segment layers in corresponding outer ETDRS sectors, particularly in the superior and temporal regions. Abnormal plasma Aβ42/40 ratio was strongly associated with worsening microvascular impairment, supporting a link between systemic amyloid pathology and retinal vascular dysfunction. Plasma ptau217 was in the indeterminate zone and not correlated with the retinal imaging metrics. Conclusions These findings demonstrate spatially concordant vascular and neuronal degeneration in the outer retina in preclinical AD. Our multimodal framework supports a biological model in which abnormal plasma Aβ42/40 (A) and plasma p-tau217 (T) values, indicative of the transitional zone to tau-mediated neuronal injury, can be interpreted with complementary spatially resolved retinal biomarkers of neurodegeneration and microvascular dysfunction to define the preclinical AD stage with greater precision.
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APA 7th
Chan, J. W., Corradetti, G., Soylu, C., Almidani, L., Wu, X., Wang, Z. C., et al. (2026). Neurovascular Outer Retinal Degeneration in Presymptomatic Alzheimer’s Disease: An Oculomic Biomarker Study. Research Square. https://doi.org/10.21203/rs.3.rs-10251231/v2
Vancouver
Chan JW, Corradetti G, Soylu C, Almidani L, Wu X, Wang ZC, et al. Neurovascular Outer Retinal Degeneration in Presymptomatic Alzheimer’s Disease: An Oculomic Biomarker Study. Research Square. 2026. doi:10.21203/rs.3.rs-10251231/v2.
BibTeX
@article{chan2026-7050e06c,
author = {Chan, J. W. and Corradetti, G. and Soylu, C. and Almidani, L. and Wu, X. and Wang, Z. C. and Astraea, N. and Hu, Z. and others},
title = {{Neurovascular Outer Retinal Degeneration in Presymptomatic Alzheimer’s Disease: An Oculomic Biomarker Study}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-10251231/v2},
url = {https://doi.org/10.21203/rs.3.rs-10251231/v2}
}
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Key findings
- Results Increased CCFD% was significantly associated with localized thinning of photoreceptor inner segment layers in corresponding outer ETDRS sectors, particularly in the superior and temporal regions.
- Abnormal plasma Aβ42/40 ratio was strongly associated with worsening microvascular impairment, supporting a link between systemic amyloid pathology and retinal vascular dysfunction.
- Conclusions These findings demonstrate spatially concordant vascular and neuronal degeneration in the outer retina in preclinical AD.
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Study details
- Study designcross-sectional
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 27 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 17 of the 62 points we could judge it on, which is 27 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 17 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 17 of the 62 points we could judge it on is 27 out of 100. |
| Total | 27 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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