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Myeloid microvesicles in cerebrospinal fluid are associated with myelin damage and neuronal loss in mild cognitive impairment and Alzheimer disease
Agosta F, Dalla Libera D, Spinelli EG, Finardi A, Canu E, Bergami A, Bocchio Chiavetto L, Baronio M et al.. Annals of neurology, 2014-10-16
Topic: Brain proteins, microglia and lab models
Objectives We have described cerebrospinal fluid (CSF) myeloid microvesicles (MVs) as a marker of microglia activation during neuroinflammation in Alzheimer disease (AD), and characterized their ability to produce toxic amyloid β1-42 (Aβ1-42 ) oligomers from aggregated or soluble substrate. The aim of this study is to investigate the association of CSF myeloid MVs with neuroimaging, clinical, and paraclinical data in AD and mild cognitive impairment (MCI). Methods We collected CSF from 106 AD patients, 51 MCI patients, and 29 neurologically healthy controls. We examined CSF myeloid MV content and AD markers. A subgroup of 34 AD and 21 MCI patients underwent structural and diffusion tensor MRI. Results Higher levels of myeloid MVs were found in the CSF of AD patients and MCI patients converting within 3 years relative to controls, but also, at a lower level, in MCI patients not converting to AD. CSF myeloid MVs were associated with Tau but not with Aβ1-42 CSF levels. CSF MVs levels correlated with white matter (WM) tract damage in MCI, and with hippocampal atrophy in AD. Interpretation Microglial MVs are neurotoxic and myelinotoxic in the presence of Aβ1-42 . CSF myeloid MVs, mirroring microglia activation and MV release, are associated with WM damage in MCI and hippocampal atrophy in AD. This suggests that hippocampal microglia activation, in the presence of Aβ1-42 in excess, produces neurotoxic and oligodendrotoxic oligomers that, through WM tract damage, spread disease to neighboring and connected areas, causing local microglia activation and propagation of disease through the same sequence of events. Ann Neurol 2014;76:813-825.
Key findings
- Results Higher levels of myeloid MVs were found in the CSF of AD patients and MCI patients converting within 3 years relative to controls, but also, at a lower level, in MCI patients not converting to AD.
- CSF myeloid MVs were associated with Tau but not with Aβ1-42 CSF levels.
- CSF myeloid MVs, mirroring microglia activation and MV release, are associated with WM damage in MCI and hippocampal atrophy in AD.
- This suggests that hippocampal microglia activation, in the presence of Aβ1-42 in excess, produces neurotoxic and oligodendrotoxic oligomers that, through WM tract damage, spread disease to neighboring and connected areas, causing local microglia activation and propagation of disease through the same sequence of events.
Why it matters
Higher levels of myeloid microvesicles were found in the cerebrospinal fluid of Alzheimer's disease patients and mild cognitive impairment patients who converted within three years, and these levels were associated with tau but not with Aβ1-42. The microvesicles correlated with white matter tract damage in mild cognitive impairment and with hippocampal atrophy in Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 47/100
Published in a leading specialty 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 | 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 | 1 / 5 | 2014 — 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 113 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.1 citations a year over 14 year(s) since 2014 |
| Impact for its field and year | 3 / 6 | Cited 3.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 2 / 4 | Cited 25 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Roberto Furlan: h-index 77 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | IRCCS Ospedale San Raffaele: institution h-index 731 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25087695) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 47 / 100 | — |
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APA 7th
Agosta, F., Dalla Libera, D., Spinelli, E. G., Finardi, A., Canu, E., Bergami, A., et al. (2014). Myeloid microvesicles in cerebrospinal fluid are associated with myelin damage and neuronal loss in mild cognitive impairment and Alzheimer disease. Annals of neurology. https://doi.org/10.1002/ana.24235
Vancouver
Agosta F, Dalla Libera D, Spinelli EG, Finardi A, Canu E, Bergami A, et al. Myeloid microvesicles in cerebrospinal fluid are associated with myelin damage and neuronal loss in mild cognitive impairment and Alzheimer disease. Annals of neurology. 2014. doi:10.1002/ana.24235. PMID: 25087695.
BibTeX
@article{agosta2014-25087695,
author = {Agosta, F. and Dalla Libera, D. and Spinelli, E. G. and Finardi, A. and Canu, E. and Bergami, A. and Bocchio Chiavetto, L. and Baronio, M. and others},
title = {{Myeloid microvesicles in cerebrospinal fluid are associated with myelin damage and neuronal loss in mild cognitive impairment and Alzheimer disease}},
journal = {Annals of neurology},
year = {2014},
doi = {10.1002/ana.24235},
pmid = {25087695},
url = {https://doi.org/10.1002/ana.24235}
}
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