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Importantly, dysregulation of Glu homeostasis has been implicated in the pathogenesis of Alzheimer\u2019s disease (AD), a neurodegenerative disorder characterized by progressive cognitive decline, neuronal loss and neuroinflammation. This review synthesizes current evidence on the biochemistry of the glutamatergic synapse, as well as the expression and signaling of Glu receptors (GluRs) in human immune cells. Furthermore, it examines two major hypotheses of AD pathogenesis \u2014the glutamatergic and the neuroimmune hypothesis\u2014 and proposes a unified glutamatergic\u2013neuroimmune framework. In this model, disrupted glutamatergic signaling at the neuron\u2013glia\u2013immune interface may represent a central contributor to AD pathology. Understanding the glutamatergic\u2013neuroimmune axis may provide novel insights into therapeutic strategies targeting neuroimmune modulation in AD.<\/jats:p>","DOI":"10.1007\/s10571-026-01784-w","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T18:44:50Z","timestamp":1785264290000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glutamate, Immune Cells and Alzheimer\u2019s Disease: An Attempt to Link the Triad"],"prefix":"10.1007","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1365-0355","authenticated-orcid":false,"given":"Nikolaos A.","family":"Chinas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8672-7619","authenticated-orcid":false,"given":"Harry","family":"Alexopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"1784_CR1","doi-asserted-by":"publisher","first-page":"1347987","DOI":"10.3389\/fnagi.2024.1347987","volume":"16","author":"A Adamu","year":"2024","unstructured":"Adamu A, Li S, Gao F, Xue G (2024) The role of neuroinflammation in neurodegenerative diseases: current understanding and future therapeutic targets. 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