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Microglial Activation and Connectivity in Alzheimer Disease and Aging
Rauchmann BS, Brendel M, Franzmeier N, Trappmann L, Zaganjori M, Ersoezlue E, Morenas-Rodriguez E, Guersel S et al.. Annals of neurology, 2022-08-25
Topic: Amyloid, tau and blood-test diagnosis
Objective Alzheimer disease (AD) is characterized by amyloid β (Aβ) plaques and neurofibrillary tau tangles, but increasing evidence suggests that neuroinflammation also plays a key role, driven by the activation of microglia. Aβ and tau pathology appear to spread along pathways of highly connected brain regions, but it remains elusive whether microglial activation follows a similar distribution pattern. Here, we assess whether connectivity is associated with microglia activation patterns. Methods We included 32 Aβ-positive early AD subjects (18 women, 14 men) and 18 Aβ-negative age-matched healthy controls (10 women, 8 men) from the prospective ActiGliA (Activity of Cerebral Networks, Amyloid and Microglia in Aging and Alzheimer's Disease) study. All participants underwent microglial activation positron emission tomography (PET) with the third-generation mitochondrial 18 kDa translocator protein (TSPO) ligand [ 18 F]GE-180 and magnetic resonance imaging (MRI) to measure resting-state functional and structural connectivity. Results We found that inter-regional covariance in TSPO-PET and standardized uptake value ratio was preferentially distributed along functionally highly connected brain regions, with MRI structural connectivity showing a weaker association with microglial activation. AD patients showed increased TSPO-PET tracer uptake bilaterally in the anterior medial temporal lobe compared to controls, and higher TSPO-PET uptake was associated with cognitive impairment and dementia severity in a disease stage-dependent manner. Interpretation Microglial activation distributes preferentially along highly connected brain regions, similar to tau pathology. These findings support the important role of microglia in neurodegeneration, and we speculate that pathology spreads throughout the brain along vulnerable connectivity pathways. ANN NEUROL 2022;92:768-781.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Rauchmann, B. S., Brendel, M., Franzmeier, N., Trappmann, L., Zaganjori, M., Ersoezlue, E., et al. (2022). Microglial Activation and Connectivity in Alzheimer Disease and Aging. Annals of neurology. https://doi.org/10.1002/ana.26465
Vancouver
Rauchmann BS, Brendel M, Franzmeier N, Trappmann L, Zaganjori M, Ersoezlue E, et al. Microglial Activation and Connectivity in Alzheimer Disease and Aging. Annals of neurology. 2022. doi:10.1002/ana.26465. PMID: 36053756.
BibTeX
@article{rauchmann2022-36053756,
author = {Rauchmann, B. S. and Brendel, M. and Franzmeier, N. and Trappmann, L. and Zaganjori, M. and Ersoezlue, E. and Morenas-Rodriguez, E. and Guersel, S. and others},
title = {{Microglial Activation and Connectivity in Alzheimer Disease and Aging}},
journal = {Annals of neurology},
year = {2022},
doi = {10.1002/ana.26465},
pmid = {36053756},
url = {https://doi.org/10.1002/ana.26465}
}
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Key findings
- Objective Alzheimer disease (AD) is characterized by amyloid β (Aβ) plaques and neurofibrillary tau tangles, but increasing evidence suggests that neuroinflammation also plays a key role, driven by the activation of microglia.
- Here, we assess whether connectivity is associated with microglia activation patterns.
- Results We found that inter-regional covariance in TSPO-PET and standardized uptake value ratio was preferentially distributed along functionally highly connected brain regions, with MRI structural connectivity showing a weaker association with microglial activation.
- AD patients showed increased TSPO-PET tracer uptake bilaterally in the anterior medial temporal lobe compared to controls, and higher TSPO-PET uptake was associated with cognitive impairment and dementia severity in a disease stage-dependent manner.
- These findings support the important role of microglia in neurodegeneration, and we speculate that pathology spreads throughout the brain along vulnerable connectivity pathways.
Why it matters
In 32 amyloid-positive early Alzheimer disease subjects and 18 amyloid-negative controls, microglial activation measured by TSPO-PET was distributed along functionally highly connected brain regions, and patients showed increased tracer uptake in some areas. This is an imaging study of microglial activation and brain connectivity, not a treatment, cure or prevention for Alzheimer's disease.
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Study details
- Participants32
- Evidence strengthLow
How this study scored 54/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Annals of neurology) |
| Journal's citation record | 3 / 4 | Annals of Neurology: journal h-index 437 (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 | 3 / 5 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 1 / 4 | 32 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 | 4 / 7 | Cited 61 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.2 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 3 / 6 | Cited 3.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 2 / 4 | Cited 45 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Robert Perneczky: h-index 73 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Imperial College London: institution h-index 1,744 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 13 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36053756) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 54 / 100 | — |
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