{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T04:48:16Z","timestamp":1792298896996,"version":"4.4.0"},"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T00:00:00Z","timestamp":1665014400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>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 \u00df2-adrenergic receptor (\u00df2-AR; i.e. agonistic autoantibodies; \u00df2-agAAb) and is linked to an elevated IOP and an impaired retinal microcirculation. As neurodegenerative disorder, Alzheimer\u2019s Disease (AD) is postulated to share a common molecular mechanism with glaucoma. In the present study we investigated autoimmune phenomena targeting the \u00df2-AR in patients with AD. Sera of the patients were analyzed in a rat cardiomyocyte bioassay for the presence of functional autoantibodies against \u00df2-AR. In addition, different species of amyloid beta (A\u00df) monomers were tested (A\u00df1-14, A\u00df10-25, A\u03b210\u201337 A\u00df1-40, A\u00df1-42, A\u03b228\u201340, and A\u00df-[Pyr]3\u201343). Our results demonstrate that none of the short-chain A\u00df (A\u00df1-14, A\u00df10-25, or A\u03b228\u201340) showed any agonistic or inhibitory effect on \u00df2-AR. Contrary, long-chain A\u00df-[Pyr]3\u201343, representing a major neurogenic plaque component, exerted an activation that after blocking by the \u00df2-AR antagonist ICI118.551, could be identified as that the effect was realized via the \u00df2-AR. Moreover, the long chain A\u00df1-40, A\u03b21\u201342, and A\u03b210\u201337, yet not the short-chain A\u00df peptides prevented the clenbuterol induced desensitization of the \u00df2-AR. In addition, we identified functional autoantibodies in the sera of AD patients, activating the \u00df2-AR, like the \u00df2-agAAb found in patients with glaucoma. As autoimmune mechanisms were reportedly involved in the pathogenesis of glaucoma and Alzheimer\u2019s Disease, we postulate that overstimulation of the \u00df2-AR pathway can induce an adrenergic overdrive, that may play an important role in the multifactorial interplay of neurodegenerative disorders.<\/jats:p>","DOI":"10.1371\/journal.pone.0272811","type":"journal-article","created":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T17:30:01Z","timestamp":1665077401000},"page":"e0272811","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Glaucoma and Alzheimer: Neurodegenerative disorders show an adrenergic dysbalance"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2546-5504","authenticated-orcid":true,"given":"Bettina","family":"Hohberger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Pr\u00fcss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Mardin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"L\u00e4mmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Wallukat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,10,6]]},"reference":[{"issue":"5","key":"pone.0272811.ref001","first-page":"691","article-title":"26 Years of the Erlangen Glaucoma Registry: Demographic and Perimetric Characteristics of Patients Through the Ages","volume":"236","author":"B Hohberger","year":"2019","journal-title":"Klinische Monatsblatter fur Augenheilkunde"},{"issue":"1","key":"pone.0272811.ref002","doi-asserted-by":"crossref","first-page":"3209","DOI":"10.1038\/s41467-018-05681-9","article-title":"Commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma","volume":"9","author":"H Chen","year":"2018","journal-title":"Nature communications"},{"issue":"4","key":"pone.0272811.ref003","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22042066","article-title":"Retinal Molecular Changes Are Associated with Neuroinflammation and Loss of RGCs in an Experimental Model of Glaucoma","volume":"22","author":"JA Fernandez-Albarral","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"1","key":"pone.0272811.ref004","doi-asserted-by":"crossref","first-page":"4890","DOI":"10.1038\/s41598-020-61848-9","article-title":"Time course of bilateral microglial activation in a mouse model of laser-induced glaucoma","volume":"10","author":"AI Ramirez","year":"2020","journal-title":"Sci Rep"},{"issue":"14","key":"pone.0272811.ref005","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1167\/iovs.61.14.18","article-title":"T and B Lymphocyte Deficiency in Rag1-\/- Mice Reduces Retinal Ganglion Cell Loss in Experimental Glaucoma","volume":"61","author":"OW Gramlich","year":"2020","journal-title":"Investigative ophthalmology & visual science"},{"issue":"5","key":"pone.0272811.ref006","doi-asserted-by":"crossref","first-page":"e0249202","DOI":"10.1371\/journal.pone.0249202","article-title":"Agonistic autoantibodies against beta2-adrenergic receptor influence retinal microcirculation in glaucoma suspects and patients","volume":"16","author":"B Hohberger","year":"2021","journal-title":"PloS one"},{"key":"pone.0272811.ref007","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3389\/fimmu.2018.00145","article-title":"Agonistic Autoantibodies to the beta2-Adrenergic Receptor Involved in the Pathogenesis of Open-Angle Glaucoma","volume":"9","author":"A Junemann","year":"2018","journal-title":"Frontiers in immunology"},{"issue":"7","key":"pone.0272811.ref008","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1007\/s00059-002-2434-z","article-title":"The beta-adrenergic receptors","volume":"27","author":"G. 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