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 beta2 adrenergic receptor (beta2-AR; i.e. agonistic autoantibodies; beta2-agAAb) and is linked to the elevated IOP and an impaired retinal microcirculation. As neurodegenerative disorder, Alzheimer Disease (AD) is postulated to share a common molecular mechanism with glaucoma. In the present study we investigated autoimmune phenomena targeting the beta2-AR in patients with AD. Sera of the patients were analyzed in a rat cardiomyocyte bioassay for the presence of functional autoantibodies against beta2-AR. In addition, different species of amyloid beta (A-beta) monomers were tested (A-beta1-14, A-beta10-25, A-beta10-37 A-beta1-40, A-beta1-42, A-beta28-40, and [Pyr]-beta3-42). Our results demonstrate that none of the short-chain A-beta (A-beta1-14, A-beta10-25, or A-beta28-40) showed any agonistic or inhibitory effect on beta2-AR. Contrary, long-chain [Pyr]-A-beta3-42, representing a major neurogenic plaque component, exerted an activation that was blocked by the beta2-AR antagonist ICI118.551 indicating that the effect was realized via the beta2-AR. Moreover, the long chain A-beta1-40, A-beta1-42, and A-beta10-37 yet not the short-chain A-beta peptides prevented the clenbuterol induced desensitization of the beta2-AR. In addition, we identified functional autoantibodies in the sera of AD patients, activating the beta2-AR like the beta2-agAAb found in patients with glaucoma. As autoimmune mechanisms were reportedly involved in the pathogenesis of glaucoma and Alzheimer Disease, we postulate that overstimulation of the beta2-AR pathway can induce an adrenergic overdrive, that may play an important role in the multifactorial interplay of neurodegenerative disorders.