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Reactive glia not only associates with plaques but also parallels tangles in Alzheimer's disease
Serrano-Pozo A, Mielke ML, Gómez-Isla T, Betensky RA, Growdon JH, Frosch MP, Hyman BT.. The American journal of pathology, 2011-07-21
Topic: Amyloid, tau and blood-test diagnosis
Senile plaques are a prominent pathological feature of Alzheimer's disease (AD), but little is understood about the association of glial cells with plaques or about the dynamics of glial responses through the disease course. We investigated the progression of reactive glial cells and their relationship with AD pathological hallmarks to test whether glial cells are linked only to amyloid deposits or also to tangle deposition, thus integrating both lesions as a marker of disease severity. We conducted a quantitative stereology-based post-mortem study on the temporal neocortex of 15 control subjects without dementia and 91 patients with AD, including measures of amyloid load, neurofibrillary tangles, reactive astrocytes, and activated microglia. We also addressed the progression of glial responses in the vicinity (≤50 μm) of dense-core plaques and tangles. Although the amyloid load reached a plateau early after symptom onset, astrocytosis and microgliosis increased linearly throughout the disease course. Moreover, glial responses correlated positively with tangle burden, whereas astrocytosis correlated negatively with cortical thickness. However, neither correlated with amyloid load. Glial responses increased linearly around existing plaques and in the vicinity of tangles. These results indicate that the progression of astrocytosis and microgliosis diverges from that of amyloid deposition, arguing against a straightforward relationship between glial cells and plaques. They also suggest that reactive glia might contribute to the ongoing neurodegeneration.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Serrano-Pozo, A., Mielke, M. L., Gómez-Isla, T., Betensky, R. A., Growdon, J. H., Frosch, M. P., et al. (2011). Reactive glia not only associates with plaques but also parallels tangles in Alzheimer's disease. The American journal of pathology. https://doi.org/10.1016/j.ajpath.2011.05.047
Vancouver
Serrano-Pozo A, Mielke ML, Gómez-Isla T, Betensky RA, Growdon JH, Frosch MP, et al. Reactive glia not only associates with plaques but also parallels tangles in Alzheimer's disease. The American journal of pathology. 2011. doi:10.1016/j.ajpath.2011.05.047. PMID: 21777559.
BibTeX
@article{serranopozo2011-21777559,
author = {Serrano-Pozo, A. and Mielke, M. L. and Gómez-Isla, T. and Betensky, R. A. and Growdon, J. H. and Frosch, M. P. and Hyman, B. T.},
title = {{Reactive glia not only associates with plaques but also parallels tangles in Alzheimer's disease}},
journal = {The American journal of pathology},
year = {2011},
doi = {10.1016/j.ajpath.2011.05.047},
pmid = {21777559},
url = {https://doi.org/10.1016/j.ajpath.2011.05.047}
}
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 names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- These results indicate that the progression of astrocytosis and microgliosis diverges from that of amyloid deposition, arguing against a straightforward relationship between glial cells and plaques.
- They also suggest that reactive glia might contribute to the ongoing neurodegeneration.
Why it matters
In brain tissue examined after death from 91 people with Alzheimer's and 15 without dementia, the amount of amyloid levelled off soon after symptoms began, but reactive astrocytes and microglia (the brain's support and immune cells) kept rising across the illness and tracked tau tangles rather than total amyloid. Glial reactions still grew around existing plaques, so the authors argue against a "straightforward" plaque–glia link and suggest reactive glia "might contribute" to ongoing nerve damage. Each brain was studied once, in one region, so this shows an association across people, not cause and effect, and it tests no treatment.
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Study details
- Participants91
- Evidence strengthLow
How this study scored 57/100
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 (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 | 2011 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 91 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 | 6 / 7 | Cited 484 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 28.5 citations a year over 17 year(s) since 2011 |
| Impact for its field and year | 4 / 6 | Cited 10.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 42 other studies in this library |
| Still being cited | 3 / 4 | Cited 106 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 | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21777559) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 57 / 100 | — |
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Read the original
- DOI: 10.1016/j.ajpath.2011.05.047
- PubMed: 21777559
- Original source →
- Free full text: American Journal Of Pathology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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