Alzheimer Disease: Kutzelnigg A

Dal Bianco A, Bradl M, Frischer J, Kutzelnigg A, Jellinger K, Lassmann H. · Center for Brain Research, Medical University of Vienna, Austria. · Ann Neurol. · Pubmed #17924575 No free full text.

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 beta-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 beta-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.

Kutzelnigg A, Lucchinetti CF, Stadelmann C, Brück W, Rauschka H, Bergmann M, Schmidbauer M, Parisi JE, Lassmann H. · Center for Brain Research, Medical University of Vienna, Vienna, Austria. · Brain. · Pubmed #16230320 links to  free full text

Abstract: Focal demyelinated plaques in white matter, which are the hallmark of multiple sclerosis pathology, only partially explain the patient's clinical deficits. We thus analysed global brain pathology in multiple sclerosis, focusing on the normal-appearing white matter (NAWM) and the cortex. Autopsy tissue from 52 multiple sclerosis patients (acute, relapsing-remitting, primary and secondary progressive multiple sclerosis) and from 30 controls was analysed using quantitative morphological techniques. New and active focal inflammatory demyelinating lesions in the white matter were mainly present in patients with acute and relapsing multiple sclerosis, while diffuse injury of the NAWM and cortical demyelination were characteristic hallmarks of primary and secondary progressive multiple sclerosis. Cortical demyelination and injury of the NAWM, reflected by diffuse axonal injury with profound microglia activation, occurred on the background of a global inflammatory response in the whole brain and meninges. There was only a marginal correlation between focal lesion load in the white matter and diffuse white matter injury, or cortical pathology, respectively. Our data suggest that multiple sclerosis starts as a focal inflammatory disease of the CNS, which gives rise to circumscribed demyelinated plaques in the white matter. With chronicity, diffuse inflammation accumulates throughout the whole brain, and is associated with slowly progressive axonal injury in the NAWM and cortical demyelination.