Glial levels determine severity of white matter disease in Alzheimer's disease:: a neuropathological study of glial changes

The morphological components of cerebral white matter disease (WMD) were studied in 17 cases of clinically diagnosed dementia and neuropathologically verified Alzheimer's disease (AD) with concomitant WMD. The distribution of grey and white matter changes was evaluated and overall as well as regional severity was graded. Total glial numbers in frontal white matter were counted using a light microscope. Oligodendrocyte and astrocyte quantities as well as astrocytic reactivity were assessed from frontal and parietal lobe white matter using a computer assisted morphometric method. The AD-WMD group was compared with 10 nondemented age-matched controls. Astrocyte/oligodendrocyte ratio (AOR) was calculated, total glial counts and AOR were compared with severity of WMD, and Alzheimer encephalopathy grade was subjectively assessed. Astrocytic numbers, AOR and astrocytic reactivity proved to be significantly higher in the demented group, whereas oligodendrocytic and total glial counts were significantly lower. Furthermore, AOR proved to be positively correlated with severity of WMD, whereas no association was found with Alzheimer encephalopathy. We conclude that WMD in dementia, for example, of the type seen in AD, can easily be detected, measured and graded quantitatively, with AOR being a significant indicator of the severity of changes. This could serve as a tool for differentiating white matter pathologies in dementia and may be the basis for recognition of the mildest white matter changes with new imaging methods, and enable potential clinical intervention.