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@INPROCEEDINGS{Gschel:283086,
      author       = {Göschel, Laura and Dell Orco, Andrea and Ittermann, Bernd
                      and Teunissen, Charlotte E. and Hoede, Patty and Melin,
                      Jeanette and Pendrill, Leslie and Roemer-Cassiano, Sebastian
                      and Franzmeier, Nicolai and Körtvelyessy, Peter and Flöel,
                      Agnes and Fillmer, Ariane},
      title        = {7{T} {MRS} {G}lutamate and {GABA} in {A}lzheimer’s
                      {D}isease},
      journal      = {Alzheimer's and dementia},
      volume       = {21},
      number       = {S7},
      issn         = {1552-5260},
      reportid     = {DZNE-2025-01493},
      pages        = {e108043},
      year         = {2025},
      abstract     = {Background: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.},
      month         = {Jul},
      date          = {2025-07-27},
      organization  = {Alzheimer’s Association
                       International Conference, Toronto
                       (Canada), 27 Jul 2025 - 31 Jul 2025},
      cin          = {AG Düzel / AG Flöel},
      ddc          = {610},
      cid          = {I:(DE-2719)5000006 / I:(DE-2719)5000081},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)1 / PUB:(DE-HGF)16},
      doi          = {10.1002/alz70861_108043},
      url          = {https://pub.dzne.de/record/283086},
}