000283086 001__ 283086 000283086 005__ 20251231103633.0 000283086 0247_ $$2doi$$a10.1002/alz70861_108043 000283086 0247_ $$2ISSN$$a1552-5260 000283086 0247_ $$2ISSN$$a1552-5279 000283086 037__ $$aDZNE-2025-01493 000283086 082__ $$a610 000283086 1001_ $$aGöschel, Laura$$b0 000283086 1112_ $$aAlzheimer’s Association International Conference$$cToronto$$d2025-07-27 - 2025-07-31$$gAAIC 25$$wCanada 000283086 245__ $$a7T MRS Glutamate and GABA in Alzheimer’s Disease 000283086 260__ $$c2025 000283086 3367_ $$0PUB:(DE-HGF)1$$2PUB:(DE-HGF)$$aAbstract$$babstract$$mabstract$$s1767100399_6286 000283086 3367_ $$033$$2EndNote$$aConference Paper 000283086 3367_ $$2BibTeX$$aINPROCEEDINGS 000283086 3367_ $$2DRIVER$$aconferenceObject 000283086 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$mjournal 000283086 3367_ $$2DataCite$$aOutput Types/Conference Abstract 000283086 3367_ $$2ORCID$$aOTHER 000283086 520__ $$aBackground:Functional neuroimaging studies suggest a dynamic trajectory in Alzheimer’s disease (AD), with early hyperconnectivity followed by hypoconnectivity due to pathologic progression. This study aimed to investigate this hypothesis using neurochemical markers derived from high-field magnetic resonance spectroscopy (MRS).Method:We analyzed data from 126 older adults enrolled in the NeuroMET studies, spanning from normal aging to dementia due to suspected AD. Using ultra-high-field 7 Tesla MRS, we quantified levels of the neurotransmitters glutamate (excitatory) and GABA (inhibitory) in the precentral cortex. Plasma p -Tau181 was used as a proxy for AD pathology, and memory was assessed using the NeuroMET Memory Metric (NMM). A p -Tau181 threshold of >2.08 pg/mL was applied as an estimated marker of amyloid positivity (Aß+). Linear mixed-effects models, adjusted for age at baseline, were used to evaluate associations and interaction effects.Result:Glutamate levels showed a non-linear association with age, decreasing up to around 70 years and increasing thereafter, while GABA levels remained stable (Figure 1A–C). Before reaching the suggested pathological conversion threshold for amyloid positivity, both glutamate and GABA showed a slight, non-significant increase in individuals with higher p -Tau181 levels (Figure 1D–F). Notably, amyloid status moderated the relationship between memory ability and glutamate levels (Figure 1G–I). Among Aß-negative individuals, lower memory ability was associated with elevated glutamate, potentially reflecting a very early compensatory response.Conclusion:Our findings support the hypothesis of a non-linear neurochemical trajectory in aging and early AD pathology. The observed age-dependent fluctuations in glutamate, together with subtle shifts in response to rising plasma p -Tau181, may reflect early pathologic or compensatory mechanisms. The interaction between glutamate and memory ability, particularly in supposedly Aß-negative individuals, suggests that excitatory neurotransmission could transiently support cognitive function in the face of emerging pathology. Notably, the threshold of plasma p -Tau181 used to define amyloid positivity may identify individuals in progressed stages, potentially missing earlier windows of therapeutic opportunity. As potential treatments may have markedly different effects depending on the stage of disease progression, investigating the trajectory of neuronal connectivity and activity is critical. 000283086 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x0 000283086 588__ $$aDataset connected to CrossRef, Journals: pub.dzne.de 000283086 7001_ $$0P:(DE-2719)9001684$$aDell Orco, Andrea$$b1$$udzne 000283086 7001_ $$aIttermann, Bernd$$b2 000283086 7001_ $$aTeunissen, Charlotte E.$$b3 000283086 7001_ $$aHoede, Patty$$b4 000283086 7001_ $$aMelin, Jeanette$$b5 000283086 7001_ $$aPendrill, Leslie$$b6 000283086 7001_ $$aRoemer-Cassiano, Sebastian$$b7 000283086 7001_ $$aFranzmeier, Nicolai$$b8 000283086 7001_ $$0P:(DE-2719)2812030$$aKörtvelyessy, Peter$$b9$$udzne 000283086 7001_ $$0P:(DE-2719)2812683$$aFlöel, Agnes$$b10$$udzne 000283086 7001_ $$aFillmer, Ariane$$b11 000283086 773__ $$0PERI:(DE-600)2201940-6$$a10.1002/alz70861_108043$$gVol. 21, no. S7, p. e108043$$nS7$$pe108043$$tAlzheimer's and dementia$$v21$$x1552-5260$$y2025 000283086 8564_ $$uhttps://pub.dzne.de/record/283086/files/DZNE-2025-1493.pdf$$yOpenAccess 000283086 8564_ $$uhttps://pub.dzne.de/record/283086/files/DZNE-2025-1493.pdf?subformat=pdfa$$xpdfa$$yOpenAccess 000283086 909CO $$ooai:pub.dzne.de:283086$$popenaire$$popen_access$$pVDB$$pdriver$$pdnbdelivery 000283086 9101_ $$0I:(DE-HGF)0$$6P:(DE-2719)9001684$$aExternal Institute$$b1$$kExtern 000283086 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812030$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b9$$kDZNE 000283086 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812683$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b10$$kDZNE 000283086 9131_ $$0G:(DE-HGF)POF4-353$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vClinical and Health Care Research$$x0 000283086 9141_ $$y2025 000283086 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2025-01-06 000283086 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2025-01-06 000283086 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0 000283086 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bALZHEIMERS DEMENT : 2022$$d2025-01-06 000283086 915__ $$0StatID:(DE-HGF)3001$$2StatID$$aDEAL Wiley$$d2025-01-06$$wger 000283086 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2025-01-06 000283086 915__ $$0StatID:(DE-HGF)9910$$2StatID$$aIF >= 10$$bALZHEIMERS DEMENT : 2022$$d2025-01-06 000283086 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2025-01-06 000283086 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess 000283086 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2025-01-06 000283086 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine$$d2025-01-06 000283086 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2025-01-06 000283086 9201_ $$0I:(DE-2719)5000006$$kAG Düzel$$lClinical Neurophysiology and Memory$$x0 000283086 9201_ $$0I:(DE-2719)5000081$$kAG Flöel$$lDementia Prevention – Mechanisms and Clinical Implementation$$x1 000283086 980__ $$aabstract 000283086 980__ $$aVDB 000283086 980__ $$aUNRESTRICTED 000283086 980__ $$ajournal 000283086 980__ $$aI:(DE-2719)5000006 000283086 980__ $$aI:(DE-2719)5000081 000283086 9801_ $$aFullTexts