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Basic Science and Pathogenesis.

Vaibhav A Janve1,2, Mabel Seto3, Hannah M Klinger4

  • 1Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 23, 2025
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Summary
This summary is machine-generated.

Phosphorylated tau 217 (pTau217) shows associations with immune and epigenetic gene pathways in preclinical Alzheimer's disease (AD). These blood-based biomarkers may improve early AD prediction.

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Area of Science:

  • Neuroscience
  • Genomics
  • Biomarker Discovery

Background:

  • Plasma pTau217 is a validated Alzheimer's disease (AD) biomarker, reflecting amyloid pathology in preclinical stages.
  • Investigating blood transcriptomic changes related to pTau217 can identify early AD indicators.
  • Quantifying blood cell populations offers insights into AD-related alterations.

Purpose of the Study:

  • To identify blood gene-network changes associated with plasma pTau217 levels in cognitively normal older adults.
  • To determine if blood cell abundance alterations correlate with plasma pTau217 levels.
  • To explore the relationship between transcriptomic data and amyloid burden.

Main Methods:

  • Whole blood RNA sequencing and plasma pTau217 data from 724 participants in the A4 Study.
  • Analysis of 20,718 genes and quantification of cell fractions using CIBERSORTx.
  • Weighted Gene Co-expression Network Analysis (WGCNA) and linear regression to identify associations with pTau217 levels.

Main Results:

  • Five gene modules showed significant associations with plasma pTau217 levels.
  • Modules related to phagocytosis, immune response, and translation were linked to pTau217.
  • Increased neutrophil abundance correlated with higher pTau217 levels.

Conclusions:

  • An association exists between immune response, epigenetic pathways, and plasma pTau217 in preclinical AD.
  • Blood transcription networks may serve as complementary biomarkers for preclinical AD prediction.
  • Further research is needed to correlate these findings with brain amyloid PET imaging.