Microglial activation in Alzheimer disease: Association with APOE genotype
Egensperger R, Kösel S, von Eitzen U, Graeber MB.. Brain pathology (Zurich, Switzerland), 1998-07-01
Topic: Amyloid, tau and blood-test diagnosis
Microglial cells are considered to play an important role in the pathogenesis of Alzheimer disease. Apart from producing the Alzheimer amyloid precursor (APP) as an acute phase protein, microglial cells seem to be involved in the deposition of its amyloidogenic cleavage product, the amyloid-beta peptide (Abeta). Abeta is bound by apolipoprotein E (APOE) in an isoform-specific manner, and it has been demonstrated that inheritance of the AD susceptibility allele, APOE epsilon4, is associated with increased deposition of Abeta in the cerebral cortex. However, the relationship between APOE epsilon4 gene dose and microglial activation is unknown. Using microglial expression of major histocompatibility complex class II molecules as a marker, we have performed a quantitative genotype-phenotype analysis on microglial activation in frontal and temporal cortices of 20 APOE genotyped AD brains. The number of activated microglia and the tissue area occupied by these cells increased significantly with APOE epsilon4 gene dose. When a model of multiple linear regression was used to compare the relative influence of APOE genotype, sex, disease duration, age at death, diffuse and neuritic plaques as well as neurofibrillary tangles on microglial activation, only APOE genotype was found to have a significant effect. Thus, the APOE gene product represents an important determinant of microglial activity in AD. Since microglial activation by APP has been shown to be modulated by apoE in vitro, a direct role of microglia in AD pathogenesis is conceivable.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Egensperger, R., Kösel, S., von Eitzen, U., & Graeber, M. B. (1998). Microglial activation in Alzheimer disease: Association with APOE genotype. Brain pathology (Zurich, Switzerland). https://doi.org/10.1111/j.1750-3639.1998.tb00166.x
Vancouver
Egensperger R, Kösel S, von Eitzen U, Graeber MB. Microglial activation in Alzheimer disease: Association with APOE genotype. Brain pathology (Zurich, Switzerland). 1998. doi:10.1111/j.1750-3639.1998.tb00166.x. PMID: 9669695.
BibTeX
@article{egensperger1998-9669695,
author = {Egensperger, R. and Kösel, S. and von Eitzen, U. and Graeber, M. B.},
title = {{Microglial activation in Alzheimer disease: Association with APOE genotype}},
journal = {Brain pathology (Zurich, Switzerland)},
year = {1998},
doi = {10.1111/j.1750-3639.1998.tb00166.x},
pmid = {9669695},
url = {https://doi.org/10.1111/j.1750-3639.1998.tb00166.x}
}
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
- Abeta is bound by apolipoprotein E (APOE) in an isoform-specific manner, and it has been demonstrated that inheritance of the AD susceptibility allele, APOE epsilon4, is associated with increased deposition of Abeta in the cerebral cortex.
- The number of activated microglia and the tissue area occupied by these cells increased significantly with APOE epsilon4 gene dose.
- When a model of multiple linear regression was used to compare the relative influence of APOE genotype, sex, disease duration, age at death, diffuse and neuritic plaques as well as neurofibrillary tangles on microglial activation, only APOE genotype was found to have a significant effect.
Why it matters
In brain tissue from 20 people with Alzheimer's disease, the number of activated microglia and the area they occupied increased significantly with the number of APOE epsilon4 alleles. This postmortem study links APOE genotype to microglial activation but does not show that targeting microglia would treat or prevent the disease.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthLow
How this study scored 43/100
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 (Brain pathology (Zurich, Switzerland)) |
| Journal's citation record | 2 / 4 | Brain Pathology: journal h-index 183 (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 | 1998 — older than 20 years, still counted |
| 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 164 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.5 citations a year over 30 year(s) since 1998 |
| Impact for its field and year | 3 / 6 | Cited 4.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 8 other studies in this library |
| Still being cited | 2 / 4 | Cited 15 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Manuel B. Graeber: h-index 72 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Ludwig-Maximilians-Universität München: institution h-index 1,224 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 9669695) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 43 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1111/j.1750-3639.1998.tb00166.x
- PubMed: 9669695
- 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 18.
Later studies that cite this one
8 studies in the alzhub library list this one in their references.
Related studies in Genetics
Also tagged “precursor”
1,339 studies in the library carry the topic tag “precursor”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,339 tagged studies.