# A systems immunology analysis of Alzheimer's disease reveals an age‐ and environmental exposure‐independent disturbance in B cell maturation

## TL;DR

This study finds that Alzheimer's disease is linked to a disturbance in B cell maturation, independent of age and environment, offering new insights into the disease's immune-related mechanisms.

## Contribution

The study identifies a novel, disease-intrinsic B cell maturation disturbance in Alzheimer's disease, independent of age and environmental factors.

## Key findings

- Alzheimer's patients show a disturbance in B cell maturation linked to disease status and cognitive decline.
- The B cell maturation disturbance is independent of age and environmental exposure.
- Additional peripheral immunological changes are associated with Alzheimer's disease.

## Abstract

Alzheimer's disease is a severe neurodegenerative disorder, with multifactorial mechanisms of disease development and progression. Evidence from genetic association studies, animal models, and clinical investigation suggests a neuroimmunological component to disease, with links to the peripheral immune system.

Here we applied a systems immunology approach to determine the immunological correlates of Alzheimer's disease. Using high‐dimensional flow cytometry and machine learning, we comprehensively assessed the cellular component of the peripheral immune system in a well‐characterized cohort of 184 Alzheimer's patients and 105 healthy spouses.

Using this approach, Alzheimer's patients demonstrated a disturbance in B cell maturation, a feature that was associated not only with disease status but also with cognitive decline. This effect was age and environmental exposure independent, suggesting a disease‐intrinsic relationship between Alzheimer's disease and B cell maturation.

These results provide an underexplored avenue for improving both mechanistic understanding and therapeutic design in Alzheimer's disease.

A systems immunology analysis on a cohort of 184 patients with Alzheimer's disease (AD) and 105 healthy spouses.AD demonstrated a defect in B cell maturation, associated with more cognitive decline.The B cell maturation association was age and environmental exposure independent.Additional peripheral immunological changes were associated with AD.

A systems immunology analysis on a cohort of 184 patients with Alzheimer's disease (AD) and 105 healthy spouses.

AD demonstrated a defect in B cell maturation, associated with more cognitive decline.

The B cell maturation association was age and environmental exposure independent.

Additional peripheral immunological changes were associated with AD.