{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T15:37:00Z","timestamp":1784907420642,"version":"3.55.0"},"reference-count":65,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"vor","delay-in-days":29,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alz &amp;amp; Dem Diag Ass &amp;amp; Dis Mo"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Gamma\u2010hydroxy\u2010butyric acid (GABA) and glutamate are neurotransmitters with essential importance for cognitive processing. Here, we investigate relationships between GABA, glutamate, and brain \u00df\u2010amyloid (A\u00df) burden before clinical manifestation of Alzheimer's disease (AD). Thirty cognitively healthy adults (age 69.9\u00a0\u00b1\u00a06 years) received high\u2010resolution atlas\u2010based <jats:sup>1<\/jats:sup>H\u2010magnetic resonance spectroscopic imaging (MRSI) at ultra\u2010high magnetic field strength of 7 Tesla for gray matter\u2010specific assessment of GABA and glutamate. We assessed A\u00df burden with positron emission tomography and risk factors for AD. Higher gray matter GABA and glutamate related to higher A\u00df\u2010burden (<jats:italic>\u00df\u00a0<\/jats:italic>=\u00a00.60, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05; <jats:italic>\u00df\u00a0<\/jats:italic>=\u00a00.64, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.02), with positive effect modification by apolipoprotein\u2010E\u2010epsilon\u20104\u2010allele (APOE4) (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.01\u20100.03). GABA and glutamate negatively related to longitudinal change in verbal episodic memory performance (<jats:italic>\u00df\u00a0<\/jats:italic>=\u00a0\u20100.48; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.02; <jats:italic>\u00df\u00a0<\/jats:italic>=\u00a0\u20100.50; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.01). In vivo measures of GABA and glutamate reflect early AD pathology at old age, in an APOE4\u2010dependent manner. GABA and glutamate may represent promising biomarkers and potential targets for early therapeutic intervention and prevention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Gray matter\u2010specific metabolic imaging with high\u2010resolution atlas\u2010based MRSI at 7 Tesla.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Higher GABA and glutamate relate to \u00df\u2010amyloid burden, in an APOE4\u2010dependent manner.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Gray matter GABA and glutamate identify older adults with high risk of future AD.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>GABA and glutamate might reflect altered synaptic and neuronal activity at early AD.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/dad2.12587","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T04:10:32Z","timestamp":1714450232000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Gray matter gamma\u2010hydroxy\u2010butyric acid and glutamate reflect beta\u2010amyloid burden at old age"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5150-6066","authenticated-orcid":false,"given":"Simon J.","family":"Schreiner","sequence":"first","affiliation":[{"name":"Institute for Regenerative Medicine University of Zurich  Zurich Switzerland"},{"name":"Department of Psychogeriatric Medicine Psychiatric University Hospital Zurich (PUK)  Zurich Switzerland"},{"name":"Department of Neurology University Hospital Zurich and University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiri M. G.","family":"Van Bergen","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton F.","family":"Gietl","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine University of Zurich  Zurich Switzerland"},{"name":"Department of Psychogeriatric Medicine Psychiatric University Hospital Zurich (PUK)  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"Buck","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine University Hospital Zurich and University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Hock","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine University of Zurich  Zurich Switzerland"},{"name":"Neurimmune  Schlieren Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaas P.","family":"Pruessmann","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Engineering University of Zurich and ETH Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Henning","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Engineering University of Zurich and ETH Zurich  Zurich Switzerland"},{"name":"High\u2010Field MR Center Max Planck Institute for Biological Cybernetics  T\u00fcbingen Germany"},{"name":"Advanced Imaging Research Center University of Texas Southwestern Medical Center  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul G.","family":"Unschuld","sequence":"additional","affiliation":[{"name":"Geriatric Psychiatry Service University Hospitals of Geneva (HUG)  Th\u00f4nex Switzerland"},{"name":"Department of Psychiatry University of Geneva (UniGE)  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