Induction of immune system mediators in the hippocampal formation in Alzheimer's and Parkinson's diseases: Selective effects on specific interleukins and interleukin receptors

Abstract

The present study determined whether molecules normally associated with immune signalling processes, specifically the lymphokines interleukin-1β, −2, −3 and −6, can be detected in the human hippocampal formation, and whether their levels are altered in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Interleukin-1β, −2, −3 and −6 were measured in post mortem tissues from 14 control neurologically normal subjects, 24 patients with Alzheimer's disease and 17 patients with Parkinson's disease. In order to assess the extent of the cholinergic deficit in the Alzheimer's disease brains, choline acetyltransferase activity in the hippocampal formation was first determined. In the Alzheimer's disease tissues, choline acetyltransferase activity was significantly reduced (by 58%) compared to the control hippocampi, whereas that in the Parkinson's disease hippocampi was not significantly different from control. Using radioimmunoassays with antisera specific for the respective interleukin, marked increases in the content of immunoreactive interleukin-1β (99%), interleukin-2 (129%) and interleukin-3 (64%) could be detected in the Alzheimer's, but not the Parkinson's disease hippocampi. Interleukin-6 levels were not significantly different in either group, compared to the control hippocampi. Since striking elevations in various interleukins were detected in the Alzheimer's disease hippocampi, the possibility that concomitant alterations in interleukin receptor sites also occurred was investigated. Using radioligand binding to hippocampal membranes, low levels of interleukin binding were measured in the control hippocampi. In the Alzheimer's tissues, significant elevations in [ 125I]interleukin-1β (by 65%) and [ 125I]interleukin-2 (by 69%) binding were noted. In contrast, [ 125I]interleukin-3 binding was not different in the Alzheimer's disease compared to the control tissues. In the hippocampal formation of Parkinson's disease brains, only [ 125I]interleukin-2 binding was significantly increased (by 80%). In summary, the present results indicate that there is pronounced activation of immune system function, particularly specific immune mediators such as the interleukins, in the hippocampal formation in Alzheimer's disease, and further suggest that stimulation of immune function may be an integral component of the pathological changes that occur in this disease.