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Association of Microglial Activation With Spontaneous ARIA-E and CSF Levels of Anti-Aβ Autoantibodies
Piazza F, Caminiti SP, Caminiti SP, Zedde M, Presotto L, DiFrancesco JC, Pascarella R, Giossi A et al.. Neurology, 2022-08-08
Topic: Brain proteins, microglia and lab models
ARIA-E can also occur spontaneously in cerebral amyloid angiopathy-related inflammation (CAA-ri), a rare autoimmune encephalopathy associated with increased CSF levels of anti-Aβ autoantibodies. Although the pathophysiologic mechanisms of ARIA-E remain to be fully elucidated, experimental evidence from ex vivo studies suggests that gantenerumab and aducanumab enable microglial activation. However, the in vivo evidence for a direct association between neuroinflammation and ARIA-E in patients with high CSF anti-Aβ (auto)antibody levels has never been demonstrated. Methods The spatial distribution and temporal variations of microglial activation associated with levels of anti-Aβ autoantibodies at (sub)acute presentation of ARIA-E and after corticosteroid therapy were evaluated in a longitudinal case series of patients with CAA-ri, the spontaneous variant of the iatrogenic ARIA-E reported in Aβ-lowering immunotherapy with monoclonal antibodies. Results At (sub)acute presentation, we found focal peaks of microglial activation having a greater spatial colocalization with ARIA-E compared with chronic age-related white matter change imaging abnormalities. The severity of ARIA-E and the magnitude of the associated microglial activation were greater in patients having AD and severe CAA concomitant disease compared with patients having CAA only. Discussion Our findings extend the current notion of ARIA-E by providing the first in vivo 11 C-PK11195 PET evidence for an association between microglial activation and the magnitude and severity of ARIA-E in patients with increased CSF concentration of anti-Aβ autoantibodies and comorbid AD and CAA disease. Our results highlight CSF testing for anti-Aβ autoantibodies as a promising diagnostic, prognostic, and therapy response biomarker to help guide future treatment and management decisions in real clinical practice and clinical trials.
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APA 7th
Piazza, F., Caminiti, S. P., Zedde, M., Presotto, L., DiFrancesco, J. C., Pascarella, R., et al. (2022). Association of Microglial Activation With Spontaneous ARIA-E and CSF Levels of Anti-Aβ Autoantibodies. Neurology. https://doi.org/10.1212/wnl.0000000000200892
Vancouver
Piazza F, Caminiti SP, Zedde M, Presotto L, DiFrancesco JC, Pascarella R, et al. Association of Microglial Activation With Spontaneous ARIA-E and CSF Levels of Anti-Aβ Autoantibodies. Neurology. 2022. doi:10.1212/wnl.0000000000200892. PMID: 35940900.
BibTeX
@article{piazza2022-35940900,
author = {Piazza, F. and Caminiti, S. P. and Zedde, M. and Presotto, L. and DiFrancesco, J. C. and Pascarella, R. and Giossi, A. and others},
title = {{Association of Microglial Activation With Spontaneous ARIA-E and CSF Levels of Anti-Aβ Autoantibodies}},
journal = {Neurology},
year = {2022},
doi = {10.1212/wnl.0000000000200892},
pmid = {35940900},
url = {https://doi.org/10.1212/wnl.0000000000200892}
}
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Key findings
- ARIA-E can also occur spontaneously in cerebral amyloid angiopathy-related inflammation (CAA-ri), a rare autoimmune encephalopathy associated with increased CSF levels of anti-Aβ autoantibodies.
- Although the pathophysiologic mechanisms of ARIA-E remain to be fully elucidated, experimental evidence from ex vivo studies suggests that gantenerumab and aducanumab enable microglial activation.
- However, the in vivo evidence for a direct association between neuroinflammation and ARIA-E in patients with high CSF anti-Aβ (auto)antibody levels has never been demonstrated.
- Methods The spatial distribution and temporal variations of microglial activation associated with levels of anti-Aβ autoantibodies at (sub)acute presentation of ARIA-E and after corticosteroid therapy were evaluated in a longitudinal case series of patients with CAA-ri, the spontaneous variant of the iatrogenic ARIA-E reported in Aβ-lowering immunotherapy with monoclonal antibodies.
- Results At (sub)acute presentation, we found focal peaks of microglial activation having a greater spatial colocalization with ARIA-E compared with chronic age-related white matter change imaging abnormalities.
Why it matters
In a longitudinal case series of patients with cerebral amyloid angiopathy-related inflammation, focal peaks of microglial activation colocalized with ARIA-E, and severity was greater in those with both Alzheimer disease and severe cerebral amyloid angiopathy. This concerns the mechanisms of a rare autoimmune encephalopathy and a side effect seen with amyloid-lowering antibodies, not a treatment, cure or prevention for Alzheimer's disease.
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Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 60/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” 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 | 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 | 4 / 7 | Cited 60 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.0 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 3 / 6 | Cited 3.4× 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 46 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Daniela Perani: h-index 78 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Milano-Bicocca: institution h-index 723 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35940900) |
| Free to read | 2 / 2 | Free to read |
| Total | 60 / 100 | — |
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