APOE ε4 linked effects on clinical features and neuropathology in dementia with Lewy bodies
Rong Ye, Anna E. Goodheart, Joseph J. Locascio, Erin Peterec, Patrick Stancu, Yanhong Wang, Stephen N. Gomperts. Alzheimer s & Dementia, 2025-10-01
Topic: Brain proteins, microglia and lab models
In analyses of APOE ε4 carriers, dosage, and genetic risk score, APOE ε4 was associated with lower odds of fluctuating cognition and parkinsonism and higher odds of visual hallucinations. APOE ε4 was associated with greater neocortical Lewy body pathology, partially mediated by AD co-pathology. The severity of fluctuating cognition was associated with Lewy body pathology stage after controlling for AD co-pathology. Visual hallucinations were associated with both Lewy body and AD pathologies. Core clinical features of DLB are sensitive to APOE haplotype. Targeting APOE biology may elucidate DLB pathogenesis and inform therapeutic development. HIGHLIGHTS: Core clinical features of dementia with Lewy bodies were sensitive to apolipoprotein E (APOE) haplotype. APOE ε4 was associated with a higher likelihood of hallucinations yet a lower likelihood of cognitive fluctuations. APOE ε4 was associated with greater severity of Lewy body pathology, partially mediated by Alzheimer's disease (AD) co-pathology. Whereas fluctuating cognition was primarily linked to Lewy body pathology, visual hallucinations were associated with both Lewy body and AD neuropathologic changes.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Ye, R., Goodheart, A. E., Locascio, J. J., Peterec, E., Stancu, P., Wang, Y., et al. (2025). APOE ε4 linked effects on clinical features and neuropathology in dementia with Lewy bodies. Alzheimer s & Dementia. https://doi.org/10.1002/alz.70795
Vancouver
Ye R, Goodheart AE, Locascio JJ, Peterec E, Stancu P, Wang Y, et al. APOE ε4 linked effects on clinical features and neuropathology in dementia with Lewy bodies. Alzheimer s & Dementia. 2025. doi:10.1002/alz.70795. PMID: 41074912.
BibTeX
@article{ye2025-41074912,
author = {Ye, Rong and Goodheart, Anna E. and Locascio, Joseph J. and Peterec, Erin and Stancu, Patrick and Wang, Yanhong and Gomperts, Stephen N.},
title = {{APOE ε4 linked effects on clinical features and neuropathology in dementia with Lewy bodies}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz.70795},
pmid = {41074912},
url = {https://doi.org/10.1002/alz.70795}
}
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Key findings
- In analyses of APOE ε4 carriers, dosage, and genetic risk score, APOE ε4 was associated with lower odds of fluctuating cognition and parkinsonism and higher odds of visual hallucinations.
- APOE ε4 was associated with greater neocortical Lewy body pathology, partially mediated by AD co-pathology.
- The severity of fluctuating cognition was associated with Lewy body pathology stage after controlling for AD co-pathology.
- Visual hallucinations were associated with both Lewy body and AD pathologies.
- Core clinical features of DLB are sensitive to APOE haplotype.
Why it matters
In dementia with Lewy bodies, APOE ε4 was linked to higher odds of visual hallucinations, lower odds of fluctuating cognition and parkinsonism, and greater neocortical Lewy body pathology partly mediated by Alzheimer co-pathology. The authors suggest targeting APOE biology may help clarify DLB pathogenesis and inform therapeutic development, but no treatment was tested.
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Study details
- Evidence strengthLow
How this study scored 39/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 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 | 1 / 7 | Cited 3 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Stephen N. Gomperts: h-index 36 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41074912) |
| Free to read | 2 / 2 | Free to read |
| Total | 39 / 100 | — |
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