Home › Research › Biomarkers
Plaque-Associated Local Toxicity Increases over the Clinical Course of Alzheimer Disease
Serrano-Pozo A, Betensky RA, Frosch MP, Hyman BT.. The American journal of pathology, 2015-12-11
Topic: Amyloid, tau and blood-test diagnosis
Amyloid (senile) plaques, one of the two pathologic hallmarks of Alzheimer disease (AD), are associated with dystrophic neurites and glial responses, both astrocytic and microglial. Although plaque burden remains relatively stable through the clinical course of AD, whether these features of local plaque toxicity continue to worsen over the course of the disease is unclear. We performed an unbiased plaque-centered quantification of SMI312(+) dystrophic neurites, GFAP(+) reactive astrocytes, and IBA1(+) and CD68(+) activated microglia in randomly selected dense-core (Thioflavin-S(+)) plaques from the temporal neocortex of 40 AD subjects with a symptom duration ranging from 4 to 20 years, and nine nondemented control subjects with dense-core plaques. Dystrophic neurites (Kendall τ = 0.34, P = 0.001), reactive astrocytes (Kendall τ = 0.30, P = 0.003), and CD68(+) (Kendall τ = 0.48, P < 0.0001), but not IBA1 microglia (Kendall τ = 0.045, P = 0.655), exhibited a significant positive correlation with symptom duration. When excluding control subjects, only the positive association between CD68(+) microglia and symptom duration remained significant (Kendall τ = 0.39, P = 0.0003). The presence of the APOEε4 allele did not affect these results. We conclude that plaques exert an increasing toxicity in the surrounding neuropil over the clinical course of AD, thereby potentially contributing to cognitive decline.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Serrano-Pozo, A., Betensky, R. A., Frosch, M. P., & Hyman, B. T. (2016). Plaque-Associated Local Toxicity Increases over the Clinical Course of Alzheimer Disease. The American journal of pathology. https://doi.org/10.1016/j.ajpath.2015.10.010
Vancouver
Serrano-Pozo A, Betensky RA, Frosch MP, Hyman BT. Plaque-Associated Local Toxicity Increases over the Clinical Course of Alzheimer Disease. The American journal of pathology. 2016. doi:10.1016/j.ajpath.2015.10.010. PMID: 26687817.
BibTeX
@article{serranopozo2016-26687817,
author = {Serrano-Pozo, A. and Betensky, R. A. and Frosch, M. P. and Hyman, B. T.},
title = {{Plaque-Associated Local Toxicity Increases over the Clinical Course of Alzheimer Disease}},
journal = {The American journal of pathology},
year = {2016},
doi = {10.1016/j.ajpath.2015.10.010},
pmid = {26687817},
url = {https://doi.org/10.1016/j.ajpath.2015.10.010}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- Amyloid (senile) plaques, one of the two pathologic hallmarks of Alzheimer disease (AD), are associated with dystrophic neurites and glial responses, both astrocytic and microglial.
- Dystrophic neurites (Kendall τ = 0.34, P = 0.001), reactive astrocytes (Kendall τ = 0.30, P = 0.003), and CD68(+) (Kendall τ = 0.48, P < 0.0001), but not IBA1 microglia (Kendall τ = 0.045, P = 0.655), exhibited a significant positive correlation with symptom duration.
- When excluding control subjects, only the positive association between CD68(+) microglia and symptom duration remained significant (Kendall τ = 0.39, P = 0.0003).
- The presence of the APOEε4 allele did not affect these results.
- We conclude that plaques exert an increasing toxicity in the surrounding neuropil over the clinical course of AD, thereby potentially contributing to cognitive decline.
Why it matters
In brain tissue from people with Alzheimer disease, dystrophic neurites, reactive astrocytes, and activated microglia around plaques increased with longer symptom duration, suggesting plaques become more toxic over the clinical course. This is a tissue study and does not test any treatment, cure, or prevention.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Evidence strengthLow
How this study scored 48/100
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 (The American journal of pathology) |
| Journal's citation record | 3 / 4 | American Journal Of Pathology: journal h-index 328 (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 | 1 / 5 | 2016 — within 20 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 | 5 / 7 | Cited 102 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.5 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 3 / 6 | Cited 4.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 2 / 4 | Cited 26 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Bradley T. Hyman: h-index 190 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26687817) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.ajpath.2015.10.010
- PubMed: 26687817
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 37.
Later studies that cite this one
4 studies in the alzhub library list this one in their references.
Related studies in Biomarkers
Also in Biomarkers
119 studies in the library are filed under Biomarkers with no topic tag they share with another; these are this study's neighbours in a fixed tour of them. The Biomarkers hub.