Abstract
Glaucoma disease is characterized by an increased intraocular pressure (IOP), glaucomatous alterations of the optic disc and corresponding visual field defects. Even lowering the main risk factor IOP until an individual target level does not prevent this neurodegenerative disorder from proceeding. Several autoimmune mechanisms were discovered, partly showing a functionality. One of these autoimmune phenomena targets the ß2 adrenergic receptor (ß2-AR; i.e. agonistic autoantibodies; ß2-agAAb) and is linked to the elevated IOP and an impaired retinal microcirculation. As neurodegenerative disorder, Alzheimer’s Disease (AD) is postulated to share a common molecular mechanism with glaucoma. In the present study we investigated autoimmune phenomena targeting the ß2-AR in patients with AD. Sera of the patients were analyzed in a rat cardiomyocyte bioassay for the presence of functional autoantibodies against ß2-AR. In addition, different species of amyloid beta (Aß) monomers were tested (Aß1-14, Aß10-25, Aβ10-37 Aß1-40, Aß1-42, Aβ28-40, and [Pyr]-Aß3-42). Our results demonstrate that none of the short-chain Aß (Aß1-14, Aß10-25, or Aβ28-40) showed any agonistic or inhibitory effect on ß2-AR. Contrary, long-chain [Pyr]-Aß3-42, representing a major neurogenic plaque component, exerted an activation that was blocked by the ß2-AR antagonist ICI118.551 indicating that the effect was realized via the ß2-AR. Moreover, the long chain Aß1-40, Aβ1-42, and Aβ10-37 yet not the short-chain Aß peptides prevented the clenbuterol induced desensitization of the ß2-AR. In addition, we identified functional autoantibodies in the sera of AD patients, activating the ß2-AR like the ß2-agAAb found in patients with glaucoma. As autoimmune mechanisms were reportedly involved in the pathogenesis of glaucoma and Alzheimer’s Disease, we postulate that overstimulation of the ß2-AR pathway can induce an adrenergic overdrive, that may play an important role in the multifactorial interplay of neurodegenerative disorders.
Competing Interest Statement
The authors have declared no competing interest.
