Clinical and pathologic correlations of machine learning quantification of Aβ deposits across 3 brain regions of decedents with Alzheimer disease
David Garcia, Shivam Rajendra Rai Sharma, Naomi Saito, Laurel A. Beckett, Louise Nicole C. Sevilla, La Rissa Vasquez, Charles S DeCarli, David Gutman et al.. Journal of Neuropathology & Experimental Neurology, 2025-12-02
Topic: Amyloid, tau and blood-test diagnosis
Machine learning enables scalable quantification of neuropathology, offering deeper phenotyping of Alzheimer's disease (AD). In this validation study, we quantified amyloid-beta (Aβ) deposits, evaluating multiple brain regions across institutions, and evaluated associations with clinical, demographic, and genetic factors in persons pathologically diagnosed with AD. All linear models were adjusted for sex, age of death, ethnicity, and center. We analyzed densities (#/mm2) of cored plaques, diffuse plaques, and cerebral amyloid angiopathy (CAA) in 273 individuals from 3 Alzheimer's Disease Research Centers. Formalin-fixed paraffin-embedded sections of frontal, temporal, and parietal cortices were immunostained and digitized, generating 799 whole-slide images (WSIs). Following log transformation, mixed-effects modeling revealed the parietal cortex had the highest cored plaque densities (P < .001); the temporal cortex had the highest diffuse plaque (P < .001); CAA showed no regional differences. Wilcoxon rank-sum test, and covariates adjusted linear models showed ApoE ε4- status was associated with higher cored plaque densities in the temporal lobe (P = .04). ApoE ε4+ status was associated with diffuse plaques in the temporal lobe (P = .001), and CAA in the frontal lobe (P = .004). These findings provide further validation and provide exploratory associations advancing deeper phenotyping of AD.
Key findings
- Following log transformation, mixed-effects modeling revealed the parietal cortex had the highest cored plaque densities (P < .001); the temporal cortex had the highest diffuse plaque (P < .001); CAA showed no regional differences.
- Wilcoxon rank-sum test, and covariates adjusted linear models showed ApoE ε4- status was associated with higher cored plaque densities in the temporal lobe (P = .04).
- ApoE ε4+ status was associated with diffuse plaques in the temporal lobe (P = .001), and CAA in the frontal lobe (P = .004).
- These findings provide further validation and provide exploratory associations advancing deeper phenotyping of AD.
Why it matters
This validation study used machine learning to quantify amyloid-beta deposits across brain regions in deceased people with Alzheimer disease, finding regional differences and associations between ApoE ε4 status and plaque types. The authors describe these as exploratory associations advancing deeper phenotyping, and no treatment, cure, or prevention is reported.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Participants273
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Neuropathology & Experimental Neurology) |
| Journal's citation record | 2 / 4 | Journal of Neuropathology & Experimental Neurology: journal h-index 239 (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 | 2 / 4 | 273 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 | 1 / 7 | Cited 2 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 0 / 4 | Cited 2 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Brittany N. Dugger: h-index 48 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California San Diego: institution h-index 1,852 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41806384) |
| Free to read | 2 / 2 | Free to read |
| Total | 43 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1093/jnen/nlaf152
- PubMed: 41806384
- Original source →
- Free full text: Journal of Neuropathology & Experimental Neurology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Garcia, D., Sharma, S. R. R., Saito, N., Beckett, L. A., Sevilla, L. N. C., Vasquez, L. R., et al. (2025). Clinical and pathologic correlations of machine learning quantification of Aβ deposits across 3 brain regions of decedents with Alzheimer disease. Journal of Neuropathology & Experimental Neurology. https://doi.org/10.1093/jnen/nlaf152
Vancouver
Garcia D, Sharma SRR, Saito N, Beckett LA, Sevilla LNC, Vasquez LR, et al. Clinical and pathologic correlations of machine learning quantification of Aβ deposits across 3 brain regions of decedents with Alzheimer disease. Journal of Neuropathology & Experimental Neurology. 2025. doi:10.1093/jnen/nlaf152. PMID: 41806384.
BibTeX
@article{garcia2025-41806384,
author = {Garcia, David and Sharma, Shivam Rajendra Rai and Saito, Naomi and Beckett, Laurel A. and Sevilla, Louise Nicole C. and Vasquez, La Rissa and DeCarli, Charles S and Gutman, David and others},
title = {{Clinical and pathologic correlations of machine learning quantification of Aβ deposits across 3 brain regions of decedents with Alzheimer disease}},
journal = {Journal of Neuropathology \& Experimental Neurology},
year = {2025},
doi = {10.1093/jnen/nlaf152},
pmid = {41806384},
url = {https://doi.org/10.1093/jnen/nlaf152}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 24.
Later studies that cite this one
1 study in the alzhub library lists this one in its references.
Related studies in Genetics
Also tagged “classification”
835 studies in the library carry the topic tag “classification”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 835 tagged studies.