Agonistic Autoantibodies to the α1-Adrenergic Receptor and the β2-Adrenergic Receptor in Alzheimer's and Vascular Dementia

Although primary causes of Alzheimers 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 Alzheimers and vascular dementia. In 59% of these patients, agonistic autoantibodies against the a1-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 Alzheimers and vascular dementia, only 17% were found to harbour these autoantibodies. The autoantibodies to the a1-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 a1-adrenergic receptor autoantibodies specifically bound to the extracellular loop1 peptide of the receptor with an apparent EC50 value of 30 nm. They mobilized intracellular calcium in a clonal cell line expressing the human form of the a1-adrenergic receptor. Our data support the notion that autoimmune mechanisms play a significant role in the pathogenesis of Alzheimers and vascular dementia. We suggest that agonistic autoantibodies to the a1-adrenergic and the beta 2-adrenergic receptor may contribute to vascular lesions and increased plaque formation.