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Basic Science and Pathogenesis.

Yang Feng1, Rafael Veiga2, Lidia Yshii3

  • 1Laboratory for Cognitive Neurology, KU Leuven, Leuven, Belgium.

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

Peripheral adaptive immunity, particularly premature B cells, shows significant changes in Alzheimer's disease (AD) patients. Reduced transitional B cells are linked to lower AD risk, highlighting their role in disease progression.

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Area of Science:

  • Immunology
  • Neuroscience
  • Systems Biology

Background:

  • Immunity plays a crucial role in Alzheimer's disease (AD) pathogenesis and progression.
  • Peripheral immune system changes, encompassing both innate and adaptive immunity, are investigated in AD.
  • Focus on individuals aged 50-80 to understand age-related immune alterations in AD.

Purpose of the Study:

  • To examine peripheral immune system changes in Alzheimer's disease (AD) patients compared to healthy controls.
  • To identify specific alterations in innate and adaptive immune cells associated with AD.
  • To assess the potential of immune profiling for AD diagnosis using machine learning.

Main Methods:

  • Utilized high-dimensional flow cytometry and systems immunology approaches.
  • Analyzed peripheral blood mononuclear cells (PBMCs) from 184 AD patients and 105 healthy controls.
  • Employed logistic regression, Mann-Whitney U tests, and a machine learning model with cross-validation for data analysis.

Main Results:

  • Reduced levels of Immature Transitional B Cells (T1), Transitional B Cells, and Transitional B Cells in Naive B Cells were observed in AD patients.
  • Non-Transitional B Cells in Naive B Cells were significantly increased in AD patients.
  • A machine learning model achieved an average AUC of 0.71, indicating good discriminative ability for AD detection.

Conclusions:

  • Peripheral adaptive immunity abnormalities in AD are primarily linked to the premature B cell compartment.
  • Specific B cell subsets show significant alterations in AD, suggesting their involvement in disease mechanisms.
  • Immune profiling of B cell subsets demonstrates potential as a biomarker for AD.