Agonistic autoantibodies to the alpha(1)-adrenergic receptor and the beta(2)-adrenergic receptor in Alzheimer's and vascular dementia

Item Type:	Article
Title:	Agonistic autoantibodies to the alpha(1)-adrenergic receptor and the beta(2)-adrenergic receptor in Alzheimer's and vascular dementia
Creators Name:	Karczewski, P. and Hempel, P. and Kunze, R. and Bimmler, M.
Abstract:	Although primary causes of Alzheimer's and vascular dementia are unknown, the importance of preceding vascular lesions is widely accepted. Furthermore, there is strong evidence for the involvement of autoimmune mechanisms. Here we report the presence of agonistic autoantibodies directed at adrenergic receptors in the circulation of patients with mild to moderate Alzheimer's and vascular dementia. In 59% of these patients agonistic autoantibodies against the alpha(1)-adrenergic receptor and the beta(2)-adrenergic receptor were identified. The majority of positive patients (66%) contained both types of autoantibodies in combination. In a control group of patients with neurological impairments others than Alzheimer's and vascular dementia, only 17% were found to harbor these autoantibodies. The autoantibodies to the alpha(1)-adrenergic receptor interacted preferably with the extracellular loop1 of the receptor. They were further studied in IgG preparations from the column regenerate of a patient who underwent immunoadsorption. The alpha(1)-adrenergic receptor autoantibodies specifically bound to the extracellular loop1 peptide of the receptor with an apparent EC(50) value of 30 nM. They mobilized intracellular calcium in a clonal cell line expressing the human form of the alpha(1)-adrenergic receptor. Our data support the notion that autoimmune mechanisms play a significant role in the pathogenesis of Alzheimer's and vascular dementia. We suggest that agonistic autoantibodies to the alpha(1)-adrenergic and the beta(2)-adrenergic receptor may contribute to vascular lesions and increased plaque formation.
Keywords:	alpha-1 Adrenergic Receptors, Alzheimer Disease, Atherosclerotic Plaque, Autoantibodies, beta-2 Adrenergic Receptors, Calcium, Cultured Cells, Immunoglobulin G, Vascular Dementia, Animals, Rats
Source:	Scandinavian Journal of Immunology
ISSN:	0300-9475
Publisher:	Wiley-Blackwell
Volume:	75
Number:	5
Page Range:	524-530
Date:	May 2012
Official Publication:	https://doi.org/10.1111/j.1365-3083.2012.02684.x
PubMed:	View item in PubMed

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