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Notably, A\u03b2 secretion is tightly linked to neuronal activity and wakefulness, and its clearance is facilitated by sleep, raising the possibility that A\u03b2 regulates sleep homeostasis. We propose that A\u03b2 functions as a cytokine-like somnogen: a molecule whose accumulation during wakefulness promotes sleep onset and maintenance via synaptic and immune mechanisms. This framework reframes A\u03b2 not as a toxic byproduct but as a key intermediary between neural activity and restorative sleep processes. We synthesize findings from molecular biology, electrophysiology, animal models, and human sleep studies, including research on A\u03b2PP processing, activity-dependent A\u03b2 release, oligomeric signaling, and the effects of anti-amyloid therapies on sleep. Particular emphasis is placed on evidence that A\u03b2 modulates synaptic excitability, engages glial immune pathways, and fulfills formal criteria for cytokine classification. Across multiple systems, A\u03b2 exhibits properties consistent with homeostatic downscaling: it dampens neurotransmitter release, suppresses excitatory receptor trafficking, and activates sleep-promoting neuronal populations. Disruption of endogenous A\u03b2PP cleavage impairs sleep consolidation, while depletion of A\u03b2 can lead to network hyperexcitability and disturbed sleep. Post-marketing reports of insomnia and abnormal dreams with plaque-clearing agents further support a physiological role. Recognizing A\u03b2 as a somnogen offers a unifying model for sleep disruption in AD and raises caution about therapies that neutralize A\u03b2 indiscriminately. Future interventions may benefit from preserving A\u03b2's homeostatic roles while mitigating its pathological aggregation.<\/jats:p>","DOI":"10.1177\/13872877251392186","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T15:34:27Z","timestamp":1762356867000},"page":"70-83","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Amyloid-\u03b2 as a cytokine-like somnogen: Rethinking its role in sleep homeostasis and Alzheimer's disease"],"prefix":"10.1177","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4288-5383","authenticated-orcid":false,"given":"Fabian-Xos\u00e9","family":"Fernandez","sequence":"first","affiliation":[{"name":"Department of Psychology, College of Science, University of Arizona, Tucson, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A","family":"Grandner","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, College of Medicine, University of Arizona, Tucson, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,11,5]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(84)80190-4"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-53839-0.00003-X"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2017.10.005"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(84)90391-1"},{"key":"e_1_3_2_6_2","article-title":"Recombinant tumor necrosis factor and interleukin 1 enhance slow-wave sleep","volume":"253","author":"Shoham S","year":"1987","unstructured":"Shoham S, Davenne D, Cady AB, et al. 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