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Retinal microvascular alterations in Alzheimer's disease: Linking blood plasma biomarkers and cerebral small vessel pathology
Kwapong WR, Wu N, Lin W, Shen J, Wang Y, Qian J, Wen C, Luan X et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025-10-01
Topic: Amyloid, tau and blood-test diagnosis
Background Retinal microvascular alterations, detectable via color fundus photography (CFP), may reflect cerebral microvascular pathology in Alzheimer's disease (AD). However, their associations with blood-based biomarkers and cerebral small vessel disease (SVD) remain unclear. Methods This cross-sectional study included 72 AD patients and 82 cognitively unimpaired (CU) controls. Participants underwent CFP, plasma biomarker analysis (amyloid beta [Aβ]42, Aβ42/40, phosphorylated tau [p-tau]181, p-tau217), and 3T magnetic resonance imaging. Retinal microvascular metrics (vessel density [VD], fractal dimension [FD]) were analyzed alongside SVD markers (white matter hyperintensities [WMHs], SVD burden) and medial temporal lobe atrophy (MTA). Results AD patients exhibited significantly reduced VD and FD compared to CU (all p < 0.001), with strong diagnostic accuracy (area under the curve: 0.969 for VD; 0.904 for FD). Retinal microvascular impairment correlated with plasma biomarkers (lower Aβ42, Aβ42/40; elevated p-tau181, p-tau217; all p < 0.05) and neuroimaging markers of SVD (WMHs, MTA; all p < 0.05). Apolipoprotein E ε4 carriers showed more severe retinal microvascular damage (p < 0.001). Discussion Retinal microvascular alterations, assayed via CFP, are linked to AD-specific proteinopathy and cerebrovascular pathology, supporting CFP as a scalable, non-invasive tool for AD biomarker discovery. Highlights Retinal microvasculature assayed via color fundus photography (CFP) is sensitive to microvascular damage and can differentiate Alzheimer's disease (AD) from cognitively unimpaired controls. Retinal microvascular damage in AD is associated with phosphorylated tau [p-tau]181, p-tau217, p-tau217/amyloid beta (Aβ)42, and increased amyloid burden (lower Aβ42 and Aβ42/40). Retinal microvascular damage in AD is associated with increased cerebral small vessel burden.
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APA 7th
Kwapong, W. R., Wu, N., Lin, W., Shen, J., Wang, Y., Qian, J., et al. (2025). Retinal microvascular alterations in Alzheimer's disease: Linking blood plasma biomarkers and cerebral small vessel pathology. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.70745
Vancouver
Kwapong WR, Wu N, Lin W, Shen J, Wang Y, Qian J, et al. Retinal microvascular alterations in Alzheimer's disease: Linking blood plasma biomarkers and cerebral small vessel pathology. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2025. doi:10.1002/alz.70745. PMID: 41065118.
BibTeX
@article{kwapong2025-41065118,
author = {Kwapong, W. R. and Wu, N. and Lin, W. and Shen, J. and Wang, Y. and Qian, J. and Wen, C. and Luan, X. and others},
title = {{Retinal microvascular alterations in Alzheimer's disease: Linking blood plasma biomarkers and cerebral small vessel pathology}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2025},
doi = {10.1002/alz.70745},
pmid = {41065118},
url = {https://doi.org/10.1002/alz.70745}
}
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Key findings
- Results AD patients exhibited significantly reduced VD and FD compared to CU (all p < 0.001), with strong diagnostic accuracy (area under the curve: 0.969 for VD; 0.904 for FD).
- Retinal microvascular damage in AD is associated with phosphorylated tau [p-tau]181, p-tau217, p-tau217/amyloid beta (Aβ)42, and increased amyloid burden (lower Aβ42 and Aβ42/40).
- Retinal microvascular damage in AD is associated with increased cerebral small vessel burden.
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Study details
- Study designcross-sectional
- Participants72
- Evidence strengthLow
How this study scored 62/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, 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 36 of the 58 points we could judge it on, which is 62 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 1 / 4 | 72 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| 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 | 2 / 2 | Indexed in PubMed (PMID 41065118) |
| Free to read | 2 / 2 | Free to read |
| Points | 36 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 36 of the 58 points we could judge it on is 62 out of 100. |
| Total | 62 / 100 | — |
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