Myeloid microvesicles in cerebrospinal fluid are associated with myelin damage and neuronal loss in mild cognitive impairment and alzheimer disease

Federica Agosta, Dacia Dalla Libera, Edoardo Gioele Spinelli, Annamaria Finardi, Elisa Canu, Alessra Bergami, Luisella Bocchio Chiavetto, Manuela Baronio, Giancarlo Comi, Gianvito Martino, Michela Matteoli, Giuseppe Magnani, Claudia Verderio, Roberto Furlan

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

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 Aβ 1-42 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.

Original languageEnglish
Pages (from-to)813-825
Number of pages13
JournalAnnals of Neurology
Volume76
Issue number6
DOIs
Publication statusPublished - Dec 1 2014

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Myelin Sheath
Cerebrospinal Fluid
Alzheimer Disease
Microglia
Amyloid
Atrophy
Cognitive Dysfunction
Diffusion Magnetic Resonance Imaging
Aptitude
Poisons
Neuroimaging

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Medicine(all)

Cite this

Myeloid microvesicles in cerebrospinal fluid are associated with myelin damage and neuronal loss in mild cognitive impairment and alzheimer disease. / Agosta, Federica; Libera, Dacia Dalla; Spinelli, Edoardo Gioele; Finardi, Annamaria; Canu, Elisa; Bergami, Alessra; Chiavetto, Luisella Bocchio; Baronio, Manuela; Comi, Giancarlo; Martino, Gianvito; Matteoli, Michela; Magnani, Giuseppe; Verderio, Claudia; Furlan, Roberto.

In: Annals of Neurology, Vol. 76, No. 6, 01.12.2014, p. 813-825.

Research output: Contribution to journalArticle

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abstract = "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 Aβ 1-42 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.",
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T1 - Myeloid microvesicles in cerebrospinal fluid are associated with myelin damage and neuronal loss in mild cognitive impairment and alzheimer disease

AU - Agosta, Federica

AU - Libera, Dacia Dalla

AU - Spinelli, Edoardo Gioele

AU - Finardi, Annamaria

AU - Canu, Elisa

AU - Bergami, Alessra

AU - Chiavetto, Luisella Bocchio

AU - Baronio, Manuela

AU - Comi, Giancarlo

AU - Martino, Gianvito

AU - Matteoli, Michela

AU - Magnani, Giuseppe

AU - Verderio, Claudia

AU - Furlan, Roberto

PY - 2014/12/1

Y1 - 2014/12/1

N2 - 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 Aβ 1-42 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.

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