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Abstract

Objective

Chronic inflammation with microglia activation is thought to play a major role in the formation or clearance of Alzheimer's disease (AD) lesions, as well as in the induction of demyelination in multiple sclerosis (MS). In MS, the cortex is severely affected by chronic, long-lasting inflammation, microglia activation, and demyelination. To what extent chronic inflammation in the cortex of MS patients influences the development of AD lesions is so far unresolved.

Methods

The study was performed on autopsy tissue of 45 MS cases, 9 AD cases, and 15 control subjects. We analyzed lymphocyte and plasma cell infiltration in relation to microglia activation, to the presence of β-amyloid plaques and (AT8+) neurofibrillary tangles, and to myelin pathology.

Results

Profound microglia activation, determined by a broad spectrum of markers, was found in both MS and AD cortices, and the patterns of microglia activation were closely similar. Microglia activation in MS cortex, in contrast with that in AD and control cortex, correlated with lymphocyte and plasma-cell infiltrates in the meninges. MS cases older than 64 years experienced development of AD pathology in comparable incidence as seen in the course of normal aging. The density of β-amyloid plaques and neurofibrillary tangles did not differ between demyelinated and nondemyelinated cortical areas.

Conclusions

Our data suggest that microglia activation in the MS cortex alone has little or no influence on the development of cortical AD pathology. Ann Neurol 2007