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Quantification of myelin loss in frontal lobe white matter in vascular dementia, Alzheimer's disease, and dementia with Lewy bodies

Ihara, Masafumi; Polvikoski, Tuomo M.; Hall, Ros; Slade, Janet Y.; Perry, Robert H.; Oakley, Arthur E.; Englund, Elisabet LU ; O'Brien, John T.; Ince, Paul G. and Kalaria, Raj N. (2010) In Acta Neuropathologica 119(5). p.579-589
Abstract
The aim of this study was to characterize myelin loss as one of the features of white matter abnormalities across three common dementing disorders. We evaluated post-mortem brain tissue from frontal and temporal lobes from 20 vascular dementia (VaD), 19 Alzheimer's disease (AD) and 31 dementia with Lewy bodies (DLB) cases and 12 comparable age controls. Images of sections stained with conventional luxol fast blue were analysed to estimate myelin attenuation by optical density. Serial adjacent sections were then immunostained for degraded myelin basic protein (dMBP) and the mean percentage area containing dMBP (%dMBP) was determined as an indicator of myelin degeneration. We further assessed the relationship between dMBP and glutathione... (More)
The aim of this study was to characterize myelin loss as one of the features of white matter abnormalities across three common dementing disorders. We evaluated post-mortem brain tissue from frontal and temporal lobes from 20 vascular dementia (VaD), 19 Alzheimer's disease (AD) and 31 dementia with Lewy bodies (DLB) cases and 12 comparable age controls. Images of sections stained with conventional luxol fast blue were analysed to estimate myelin attenuation by optical density. Serial adjacent sections were then immunostained for degraded myelin basic protein (dMBP) and the mean percentage area containing dMBP (%dMBP) was determined as an indicator of myelin degeneration. We further assessed the relationship between dMBP and glutathione S-transferase (a marker of mature oligodendrocytes) immunoreactivities. Pathological diagnosis significantly affected the frontal but not temporal lobe myelin attenuation: myelin density was most reduced in VaD compared to AD and DLB, which still significantly exhibited lower myelin density compared to ageing controls. Consistent with this, the degree of myelin loss was correlated with greater %dMBP, with the highest %dMBP in VaD compared to the other groups. The %dMBP was inversely correlated with the mean size of oligodendrocytes in VaD, whereas it was positively correlated with their density in AD. A two-tier regression model analysis confirmed that the type of disorder (VaD or AD) determines the relationship between %dMBP and the size or density of oligodendrocytes across the cases. Our findings, attested by the use of three markers, suggest that myelin loss may evolve in parallel with shrunken oligodendrocytes in VaD but their increased density in AD, highlighting partially different mechanisms are associated with myelin degeneration, which could originate from hypoxic-ischaemic damage to oligodendrocytes in VaD whereas secondary to axonal degeneration in AD. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Oligodendrocyte, Myelin basic protein, Alzheimer's disease, Myelin, White matter, Vascular dementia
in
Acta Neuropathologica
volume
119
issue
5
pages
579 - 589
publisher
Springer
external identifiers
  • wos:000276353400005
  • scopus:77953025222
ISSN
1432-0533
DOI
10.1007/s00401-009-0635-8
language
English
LU publication?
yes
id
54519168-820a-4cc8-ab30-e2add37c52ab (old id 1603988)
date added to LUP
2010-05-18 15:46:50
date last changed
2018-06-24 04:20:06
@article{54519168-820a-4cc8-ab30-e2add37c52ab,
  abstract     = {The aim of this study was to characterize myelin loss as one of the features of white matter abnormalities across three common dementing disorders. We evaluated post-mortem brain tissue from frontal and temporal lobes from 20 vascular dementia (VaD), 19 Alzheimer's disease (AD) and 31 dementia with Lewy bodies (DLB) cases and 12 comparable age controls. Images of sections stained with conventional luxol fast blue were analysed to estimate myelin attenuation by optical density. Serial adjacent sections were then immunostained for degraded myelin basic protein (dMBP) and the mean percentage area containing dMBP (%dMBP) was determined as an indicator of myelin degeneration. We further assessed the relationship between dMBP and glutathione S-transferase (a marker of mature oligodendrocytes) immunoreactivities. Pathological diagnosis significantly affected the frontal but not temporal lobe myelin attenuation: myelin density was most reduced in VaD compared to AD and DLB, which still significantly exhibited lower myelin density compared to ageing controls. Consistent with this, the degree of myelin loss was correlated with greater %dMBP, with the highest %dMBP in VaD compared to the other groups. The %dMBP was inversely correlated with the mean size of oligodendrocytes in VaD, whereas it was positively correlated with their density in AD. A two-tier regression model analysis confirmed that the type of disorder (VaD or AD) determines the relationship between %dMBP and the size or density of oligodendrocytes across the cases. Our findings, attested by the use of three markers, suggest that myelin loss may evolve in parallel with shrunken oligodendrocytes in VaD but their increased density in AD, highlighting partially different mechanisms are associated with myelin degeneration, which could originate from hypoxic-ischaemic damage to oligodendrocytes in VaD whereas secondary to axonal degeneration in AD.},
  author       = {Ihara, Masafumi and Polvikoski, Tuomo M. and Hall, Ros and Slade, Janet Y. and Perry, Robert H. and Oakley, Arthur E. and Englund, Elisabet and O'Brien, John T. and Ince, Paul G. and Kalaria, Raj N.},
  issn         = {1432-0533},
  keyword      = {Oligodendrocyte,Myelin basic protein,Alzheimer's disease,Myelin,White matter,Vascular dementia},
  language     = {eng},
  number       = {5},
  pages        = {579--589},
  publisher    = {Springer},
  series       = {Acta Neuropathologica},
  title        = {Quantification of myelin loss in frontal lobe white matter in vascular dementia, Alzheimer's disease, and dementia with Lewy bodies},
  url          = {http://dx.doi.org/10.1007/s00401-009-0635-8},
  volume       = {119},
  year         = {2010},
}