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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
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Biomarkers.

Jiabin Tang1, Kishan Patel1, Jiaxin Xiang1

  • 1Weill Cornell Medicine, New York, NY, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
PubMed
Summary
This summary is machine-generated.

Early Alzheimer's Disease (AD) involves increased neuronal hyperexcitability due to re-expressed voltage-gated sodium channel Nav1.3, particularly in female mice, impacting hippocampal CA3 activity.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pathology

Background:

  • Neuronal hyperexcitability is a key feature in early Alzheimer's Disease (AD), contributing to cognitive decline.
  • The precise molecular mechanisms driving AD-related hyperexcitability remain incompletely understood.
  • Voltage-gated sodium channel (Nav) subtype expression influences neuronal network excitability, with developmental stage impacting susceptibility.

Purpose of the Study:

  • To investigate the hypothesis that developmentally dominant Nav1.3 is re-expressed in Alzheimer's Disease (AD).
  • To determine if re-expressed Nav1.3 potentiates hippocampal CA3 hyperexcitability in early AD.
  • To explore sex-dependent differences in AD-related hyperexcitability.

Main Methods:

  • Quantified Nav1.3 expression in mossy fiber terminals using immunogold labeling and electron microscopy in wildtype and 5xFAD mice at different ages.
  • Measured real-time neuronal activity in hippocampal CA3 neurons via fiber photometry.
  • Assessed Nav1.3 neurophysiological properties using electrophysiology.

Main Results:

  • Early-stage AD mice exhibited increased Nav1.3 labeling in mossy terminals and heightened hippocampal CA3 neuronal activity compared to controls.
  • Neuronal activation was more pronounced in female mice during the early stages of AD.
  • Nav1.3 expression and activity correlated with hyperexcitability in the CA3 region.

Conclusions:

  • Identified Nav1.3 as a novel voltage-gated sodium channel subtype re-expressed in early Alzheimer's Disease.
  • Demonstrated that Nav1.3 re-expression contributes to hippocampal CA3 hyperexcitability in early AD.
  • Highlighted sex-dependent differences in AD-related hyperexcitability, with females showing greater activation.