Expression of the histocompatibility glycoprotein HLA-DR in neurological disease

Abstract

Reactive microglia or macrophages expressing the histocompatibility glycoprotein HLA-DR were detected in many neurological diseases including Alzheimer's, Parkinson's, Pick's and Huntington's diseases, parkinsonism-dementia of Guam, amyotrophic lateral sclerosis, Shy-Drager syndrome, multiple sclerosis and AIDS encephalopathy. Reactive astrocytes, also present in these conditions, were established as a population distinct from the HLA-DR positive microglia by double immunostaining for glial fibrillary acidic protein and HLA-DR. A distinctive pattern of HLA-DR positive cells was seen in each disease entity. Areas known to contain pathology always stained positively, and, in several cases, reactive microglia appeared in areas that would otherwise not have been suspected of being involved in the pathological process. HLA-DR staining, which outlines the surface membranes of positive cells, was so strong that lesioned areas could frequently be identified in sections with the naked eye. In adjacent sections stained with H&E or sections destained of HLA-DR and then restained with H&E, gliosis was often hard to identify except on close microscopic inspection. The results suggest that HLA-DR staining may be a valuable addition to standard neuropathological methods and might be useful in investigating diseases where pathology has not yet been identified.

Role of microglia in CNS inflammation

“…The enormous interest in inflammation in AD is comparable to that in PD and has a similar historical background [21,22,37]. The driving motivation is also similar, i.e., to develop anti-inflammatory therapies that, while they may not cure AD, will hopefully help slow the progression or delay the onset of this disorder [38].…”

Lipopolysaccharide-Induced Inflammation Exacerbates Tau Pathology by a Cyclin-Dependent Kinase 5-Mediated Pathway in a Transgenic Model of Alzheimer's Disease

“…Other degenerative changes occur as well, including progressive neuronal and synaptic loss and a reduction in selective neurotransmitter systems (DeKosky and Scheff, 1990;Terry et al, 1991;Dringenberg, 2000). The activation of inflammatory cells is another prominent feature that is performed by microglia and astrocytes, and there is ample evidence showing that these cells are upregulated in the AD brain as well as in transgenic animals (McGeer et al, 1988;Frautschy et al, 1998;Akiyama et al, 2000;Sasaki et al, 2002).…”

The executioners sing a new song: killer caspases activate microglia

“…2 The first indications for a role of inflammation in the pathogenesis of PD came from studies demonstrating the presence of cytotoxic T-lymphocytes and reactive microglia in the parkinsonian brain. 4,5 Studies on brains from humans 4 who had self-administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and monkeys 6 receiving the same toxin, revealed a striking microglial activation along with significant accumulation of extraneuronal neuromelanin, which can activate microglia. These findings established that an acute neurotoxic insult to the nigrostriatal system can result in longterm inflammatory response involving a reactive microgliosis and possibly leading to a self-perpetuating process of neurodegeneration.…”