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Histopathologic correlates of white matter changes on MRI in Alzheimer's disease and normal aging
P Scheltens1, F Barkhof, D Leys
1Department of Neurology, Academisch Ziekenhuis VU, Amsterdam, The Netherlands.
Abstract:
We investigated the histopathologic correlates of white matter changes in Alzheimer's disease (AD) patients (n = 6) and controls (n = 9) using postmortem MRI. White matter changes were rated on a 0 to 3 scale in 51 regions. Histopathologically, we subjectively rated the loss of myelinated axons in the deep and periventricular white matter, denudation of the ventricular ependyma, gliosis, width of the perivascular spaces, and leptomeningeal congophilic angiopathy; we measured structural changes in the walls of the blood vessels in the white matter in micrometers. The AD brains displayed significantly more white matter hyperintensities on MRI than controls. Histopathologically, the denudation of the ventricular ependyma and the gliosis were significantly more severe in AD than in controls, and there was a trend toward more loss of myelinated axons in the deep white matter in the AD brains (p = 0.07). The MRI abnormalities correlated with the loss of myelinated axons in the deep white matter (r' = 0.37; p < 0.01) and with the denudation of the ventricular lining (r' = 0.54; p < 0.01). We could not find any evidence for arteriolosclerosis, but the mean thickness of the adventitia of the arteries of the deep white matter in AD almost doubled the value in control brains (p = 0.0009). We conclude that white matter abnormalities in AD patients and controls consist of loss of myelinated axons, probably caused by arterial changes and breakdown of the ventricular lining. Since imaging/histopathologic correlation was similar in AD patients and controls, these changes probably represent some form of accelerated aging.
Insights
Alzheimer's disease (AD) brains show more white matter changes, including axon loss and ventricular lining damage, compared to controls. These histopathologic findings correlate with MRI abnormalities, suggesting accelerated aging.
Area of Science:
- Neuropathology
- Neuroimaging
- Gerontology
Background:
- White matter changes are observed in Alzheimer's disease (AD) but their histopathologic basis requires further investigation.
- Understanding these changes is crucial for diagnosing and potentially treating AD.
Purpose of the Study:
- To investigate the histopathologic correlates of white matter changes seen on postmortem MRI in Alzheimer's disease (AD) patients and controls.
- To compare the severity of specific white matter pathologies between AD and control groups.
Main Methods:
- Postmortem MRI was used to assess white matter changes in 6 AD patients and 9 controls.
- Histopathologic examination included ratings of myelinated axon loss, ventricular ependymal denudation, gliosis, perivascular space width, and leptomeningeal angiopathy.
- Vessel wall structural changes in white matter arteries were measured.
Main Results:
- AD brains exhibited significantly more white matter hyperintensities on MRI compared to controls.
- Histopathology revealed more severe ventricular ependymal denudation and gliosis in AD brains.
- MRI abnormalities correlated significantly with loss of myelinated axons and ventricular lining denudation.
- Arterial adventitia thickness in the deep white matter was significantly increased in AD patients.
Conclusions:
- White matter abnormalities in AD and controls involve loss of myelinated axons, likely due to arterial changes and ventricular lining breakdown.
- The similar imaging-histopathologic correlations in both groups suggest these changes represent a form of accelerated aging.
- These findings highlight the importance of vascular integrity in white matter health and its implications for neurodegenerative diseases.