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Updated: Jan 7, 2026

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

Simonetta Falzoni1, Mario Tarantini1, Nelly Redolfi2

  • 1University of Ferrara, FERRARA, Ferrara, Italy.

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

Extracellular ATP (eATP) fuels neuroinflammation in Alzheimer's disease (AD). Elevated plasma shed P2X7 receptor (sP2X7R) levels in mild cognitive impairment (MCI) suggest it may be an early biomarker for AD progression.

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Area of Science:

  • Neuroscience
  • Immunology
  • Biochemistry

Background:

  • Neuroinflammation, a key factor in Alzheimer's Disease (AD), is sustained by elevated extracellular ATP (eATP) in the brain.
  • The P2X7 receptor (P2X7R), a receptor for eATP, is expressed by immune cells and activates the NLRP3 inflammasome, releasing inflammatory mediators.
  • A plasma shed form of P2X7R (sP2X7R) has been identified and found to be elevated in inflammatory conditions.

Purpose of the Study:

  • To measure eATP levels in the brain of an AD mouse model using novel luminescent probes.
  • To investigate the expression of P2X7R, NLRP3, and inflammatory cytokines in the AD mouse brain.
  • To determine if sP2X7R levels are elevated in human plasma samples from individuals with mild cognitive impairment (MCI) and AD.

Main Methods:

  • Extracellular ATP (eATP) brain levels were measured in an AD mouse model using the pmeLUC luminescent probe via retro-orbital sinus injection.
  • Levels of P2X7R, NLRP3, and inflammatory cytokines (IL-1β, IL-6, TNF-α) were quantified in cortical homogenates.
  • Plasma sP2X7R concentrations were measured by ELISA in healthy controls (HC), MCI patients, and AD patients.

Main Results:

  • Significantly higher eATP levels were detected in the brains of AD mice compared to age-matched controls, evident as early as 2 months of age, preceding Aβ plaque deposition.
  • The cytokine profile indicated that neuroinflammation accompanies AD progression and begins before Aβ plaque deposition.
  • Plasma sP2X7R concentrations were significantly increased in MCI patients compared to HC subjects. AD patients showed higher sP2X7R than controls, though not reaching statistical significance.

Conclusions:

  • The findings strongly support the contribution of eATP to neuroinflammation in Alzheimer's Disease.
  • Plasma shed P2X7R (sP2X7R) shows promise as a biomarker for identifying early stages of cognitive impairment that may progress to dementia.
  • This research was funded by the Cure Alzheimer's Fund.