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Peer-reviewedCC BYInternational journal of molecular sciences

Sex-Divergent Patterns in Hippocampal and Cortical NMDA Receptor Density Across the Alzheimer's Disease Continuum.

  • Maricedes Acosta-Martínez1
  • Vanessa Carter2
  • Aviram Nessim1
  • Sarah Murphy1
  • Jasbeer Dhawan2
  • Thomas G Beach3
  • Geidy E Serrano3
  • Erin E Sundermann4
  • Anat Biegon2
4 affiliations
  1. 1Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY 11794, USA.
  2. 2Department of Radiology, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY 11794, USA.
  3. 3Banner Sun Health Research Institute, Sun City, AZ 85351, USA.
  4. 4Department of Psychiatry, University of California, San Diego, CA 92093, USA.
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Abstract

While the loss of NMDA receptors (NMDARs) is associated with Alzheimer's disease (AD) severity, the effect of sex or the relationship between regional NMDAR density and antemortem cognitive status across the AD spectrum has not been examined. We performed quantitative in vitro autoradiography of the hippocampus, entorhinal cortex (EC), and parietal cortex using NMDAR and tau radioligands. Relationships between regional NMDAR density and cognitive status assessed by the Mini Mental State Examination (MMSE), and between NMDAR and tau density, were examined by bivariate correlations. In both sexes, the largest AD-related decreases in NMDAR density were observed in the cornu ammonis 1 (CA1) field. However, there was a significant diagnosis by sex interaction driven by sex-specific differences in the mild cognitive impairment (MCI) stage, with lower NMDAR density in MCI women, but not MCI men relative to same-sex controls. Within diagnosis analyses revealed positive correlations between NMDAR density and MMSE scores and significant negative correlations between EC NMDAR and tau density, which was significant only in AD men. Our data show that differences in hippocampal NMDAR density across the AD continuum are modulated by sex and may contribute to the known sex differences in the clinical trajectory of the disease.

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Cite

BibTeXRIS
BibTeX
@article{acostamartinez2026sexdivergent,
  title = {{Sex-Divergent Patterns in Hippocampal and Cortical NMDA Receptor Density Across the Alzheimer's Disease Continuum.}},
  author = {Maricedes Acosta-Martínez and Vanessa Carter and Aviram Nessim and Sarah Murphy and Jasbeer Dhawan and Thomas G Beach and Geidy E Serrano and Erin E Sundermann and Anat Biegon},
  journal = {International journal of molecular sciences},
  year = {2026},
  month = sep,
  doi = {10.3390/ijms27198590},
  url = {https://europepmc.org/article/MED/42883839},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Sex-Divergent Patterns in Hippocampal and Cortical NMDA Receptor Density Across the Alzheimer's Disease Continuum.
AU  - Maricedes Acosta-Martínez
AU  - Vanessa Carter
AU  - Aviram Nessim
AU  - Sarah Murphy
AU  - Jasbeer Dhawan
AU  - Thomas G Beach
AU  - Geidy E Serrano
AU  - Erin E Sundermann
AU  - Anat Biegon
PY  - 2026
DA  - 2026/09/25
JO  - International journal of molecular sciences
DO  - 10.3390/ijms27198590
UR  - https://europepmc.org/article/MED/42883839
AB  - While the loss of NMDA receptors (NMDARs) is associated with Alzheimer's disease (AD) severity, the effect of sex or the relationship between regional NMDAR density and antemortem cognitive status across the AD spectrum has not been examined. We performed quantitative in vitro autoradiography of the hippocampus, entorhinal cortex (EC), and parietal cortex using NMDAR and tau radioligands. Relationships between regional NMDAR density and cognitive status assessed by the Mini Mental State Examination (MMSE), and between NMDAR and tau density, were examined by bivariate correlations. In both sexes, the largest AD-related decreases in NMDAR density were observed in the cornu ammonis 1 (CA1) field. However, there was a significant diagnosis by sex interaction driven by sex-specific differences in the mild cognitive impairment (MCI) stage, with lower NMDAR density in MCI women, but not MCI men relative to same-sex controls. Within diagnosis analyses revealed positive correlations between NMDAR density and MMSE scores and significant negative correlations between EC NMDAR and tau density, which was significant only in AD men. Our data show that differences in hippocampal NMDAR density across the AD continuum are modulated by sex and may contribute to the known sex differences in the clinical trajectory of the disease.
SN  - 1422-0067
ER  -