We detected large numbers of HLA-DR-positive reactive microglia (macrophages), along with Lewy bodies and free melanin, in the substantia nigra of all cases studied with Parkinson's disease (5) and parkinsonism with dementia (PD) (5). We found similar, but less extensive, pathology in the substantia nigra of six of nine cases of dementia of the Alzheimer type (DAT) but in only one of 11 age-matched nonneurologic cases. All dementia cases with a premortem diagnosis of DAT or PD showed large numbers of HLA-DR-positive reactive microglia and significant plaque and tangle counts in the hippocampus, as well as reduced cortical choline acetyltransferase activity. One of 11 nondemented controls showed mild evidence of similar cortical pathology. These data indicate that HLA-DR-positive reactive microglia are a sensitive index of neuropathologic activity. They suggest a frequent coexistence of DAT- and Parkinson-type pathology in elderly patients.

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It has been hypothesized that idiopathic parkinsonism might be due to age-related attrition of dopamine neurons occurring long after an initial acute episode. We present evidence against this hypothesis, based on our finding of at least six times as many HLA-DR-positive microglia phagocytosing dopamine neurons in parkinsonian brains as in control brains. This difference indicates an active pathological process.

Involvement of the immune system in the pathogenesis of Alzheimer's disease was demonstrated in two ways: by the attachment of complement proteins to diseased tissue, and by the activation of cells associated with the immune system. Alzheimer brain tissue was stained immunohistochemically by antibodies to components of the classical, but not the alternative, complement pathway. Antibodies to Clq, C3d, and C4d stained senile plaques, dystrophic neurites, neuropil threads and some tangled neurons. Antibodies to a neoantigenic site on the C5b-9 membrane attack complex stained dystrophic neurites and many tangled neurons, but not senile plaques. Antibodies to Factor P and fraction Bb of Factor B, which are specific for the alternative complement pathway, did not stain Alzheimer brain tissue. The cellular immune response was evaluated by the presence of reactive microglia and by the infiltration of small numbers of T-cells into diseased brain tissue. Reactive microglia were identified by antibodies to HLA-DR, a class II major histocompatibility complex glycoprotein, and by enhanced staining with antibodies to leukocyte common antigen and the FC7RI and FcyRII receptors. T-cells were identified by antibodies to leukocyte common antigen, as well as the CD4 and CD8 surface proteins. Double immunostaining with antibodies to GFAP and MHC class I or class II antigens established that astrocytes, which are GFAP positive, do not express MHC antigens in Alzheimer's disease. Endothelial cells express MHC class I antigens while reactive microglia and some leukocytes express class II antigen. RESUME: La reponse immunitaire dans la maladie d'Alzheimer L'implication du systeme immunitaire dans la pathogenese de la maladie d'Alzheimer a ete demontree de deux facons: par la fixation de proteines du complement au niveau du tissu atteint et par l'activation de cellules associees au systeme immunitaire. Le tissu cerebral de patients atteints de la maladie d'Alzheimer (MA) a ete colore par immunohistochimie au moyen d'anticorps diriges contre des composantes de la voie classique, et non de la voie alterne, d'activation du complement. Les anticorps diriges contre Clq, C3d et C4d coloraient les plaques seniles, les neurites dystrophiques, les fils neuropiles et quelques neurones contenant des amas neurofibrillaires. Des anticorps a un site neo-antigenique sur le complexe s'attaquant a la membrane C5b-9 colorait des neurites dystrophiques et plusieurs neurones contenant des amas neurofibrillaires, et non les plaques seniles. Les anticorps au Facteur P et la fraction Bb du Facteur B, qui sont specifiques pour la voie alterne d'activation du complement, ne coloraient pas le tissu cerebral de patients atteint de MA. La reponse immunitaire cerebrale a ete eValuee par la presence de microglie reactionnelle et par l'infiltration d'un petit nombre de cellules T dans le tissu cerebral malade. La microglie reactionnelle a ete identified par des anticorps diriges contre le HLA-DR une glycoproteine de classe II du complexe majeur d'histocomp...