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

Acta Neuropathol 2010 May 21;119(5):579-89. Epub 2010 Jan 21.

Institute for Ageing and Health, Wolfson Research Centre, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UK.

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.

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http://dx.doi.org/10.1007/s00401-009-0635-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849937PMC
May 2010
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References

(Supplied by CrossRef)

I Akiguchi et al.
Stroke 1997

I Akiguchi et al.
Acta Neuropathol 2004

I Alafuzoff et al.
Acta Neuropathol 2009

SI Bannykh et al.
J Neurooncol 2006

R Barber et al.
J Neurol Neurosurg Psychiatry 1999

G Bartzokis et al.
Neurobiol Aging 2004

M Bozzali et al.
Brain 2005

H Braak et al.
Acta Neuropathol 2006

H Braak et al.
Acta Neuropathol 1991

EJ Burton et al.
Stroke 2004

EJ Burton et al.
Am J Geriatr Psychiatry 2006

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