title: Myeloid microvesicles in cerebrospinal fluid are associated with myelin damage and neuronal loss in mild cognitive impairment and Alzheimer disease.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Neuroscience, Institute of Experimental Neurology, Scientific Institute San Raffaele, Milan.
authors.forename: Federica
authors.initials: F
authors.lastname: Agosta
authors.forename: Dacia
authors.initials: D
authors.lastname: Dalla Libera
authors.forename: Edoardo Gioele
authors.initials: EG
authors.lastname: Spinelli
authors.forename: Annamaria
authors.initials: A
authors.lastname: Finardi
authors.forename: Elisa
authors.initials: E
authors.lastname: Canu
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bergami
authors.forename: Luisella
authors.initials: L
authors.lastname: Bocchio Chiavetto
authors.forename: Manuela
authors.initials: M
authors.lastname: Baronio
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.forename: Gianvito
authors.initials: G
authors.lastname: Martino
authors.forename: Michela
authors.initials: M
authors.lastname: Matteoli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Magnani
authors.forename: Claudia
authors.initials: C
authors.lastname: Verderio
authors.forename: Roberto
authors.initials: R
authors.lastname: Furlan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002452:Cell Count / Q000379:methods; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009186:Myelin Sheath / Q000378:metabolism* / Q000473:pathology; D022423:Myeloid Cells / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology
chemical_list: D015415:Biomarkers